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Viral Infections (viral + infections)
Kinds of Viral Infections Selected AbstractsPrison Officers' Concerns About Blood Borne Viral InfectionsTHE HOWARD JOURNAL OF CRIMINAL JUSTICE, Issue 1 2005Brendan Dillon Most officers (87%) reported not knowing enough about these diseases to enable them to take the necessary precautions at work. Longer serving and senior officers were less fearful and less anxious about contracting the infections. Officers who had received hepatitis B vaccination were no less worried about hepatitis B than unvaccinated colleagues. Training on blood borne viruses had little effect on prison officers' knowledge or perception of blood borne viral infections. [source] RNA Respiratory Viral Infections in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2009M. G. Ison First page of article [source] Viral infections as potential triggers of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2007Nienke van der Werf Abstract During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct ,-cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes-susceptible individuals in order to delay or even prevent the diabetogenic process. Copyright © 2007 John Wiley & Sons, Ltd. [source] Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus-68EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003James Abstract Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus-68 (,HV-68) to exacerbate development of neurological symptoms. SJL mice received UV-inactivated ,HV-68 or intranasal,HV-68, followed by immunization against proteolipid-protein peptide 139,151. Infected mice became moribund within 10,days post-immunization, whereas mice exposed to UV-inactivated ,HV-68 recovered. In the second model, Lewis rats were exposed to UV-inactivated ,HV-68 or to ,HV-68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent ,HV-68 infection. It is unlikely that this ,HV-68-induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious-centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system. [source] Mechanisms of virus-induced asthma exacerbations: state-of-the-art.ALLERGY, Issue 5 2007A GA2LEN, InterAirways document Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research. [source] Viral infections in the mouthORAL DISEASES, Issue 2002CG Teo Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein,Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via non-glossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis. [source] Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocolPEDIATRIC BLOOD & CANCER, Issue 5 2004G. Acquatella MD Abstract Background We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. Procedure Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). Results Mean follow-up was 35,±,31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. Toxicity: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). Conclusions The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program. © 2004 Wiley-Liss, Inc. [source] Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic,PEDIATRIC PULMONOLOGY, Issue 12 2006Hanne Vebert Olesen MD Abstract Background Respiratory viral and atypical bacterial infections are associated with pulmonary exacerbations and hospitalisations in cystic fibrosis patients. We wanted to study the impact of such infections on children attending the outpatient clinic. Methods Seventy-five children were followed for 12 months at regular clinic visits. Routine sputum/laryngeal aspirations were tested with PCR for 7 respiratory viruses. Antibodies against C. pneumoniae, M. pneumoniae and B. pertussis were measured every 3,4 months. FEV-1, FEF25,75 and specific airway resistance, "viral" symptoms and bacterial culture were recorded. Results Ninety-seven viral and 21 atypical bacterial infections were found. FEV-1 was significantly reduced during viral infection (,12.5%, p=0.048), with the exception of rhinovirus infection. A small change in FEV-1 (,3%) was seen during atypical bacterial infection (p=0.039). Viral and atypical bacterial infections caused no change in type and frequency of bacterial culture. Positive predictive value of "viral symptoms" was low (0.64%). Eight patients received "unnecessary" antibiotics because of viral symptoms. Conclusions Some viral infections and atypical bacterial infections affect FEV-1 acutely. Viral infections did not precipitate bacterial infection or change of colonisation. Clinical symptoms failed to diagnose viral infection accurately. Routine surveillance for virus or atypical bacteria seems not to be justified in this patient category. Pediatr Pulmonol. 2006; 41:1197,1204. © 2006 Wiley-Liss, Inc. [source] Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesisPEDIATRIC TRANSPLANTATION, Issue 4 2003Amira Al-Uzri Abstract: Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein,Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient. [source] Rhinovirus is not detectable in peripheral lung tissue after asthma deathRESPIROLOGY, Issue 2 2003Mark W. WATSON Objective: Viral infections are associated with both mild and severe exacerbations of asthma and may therefore be associated with asthma death. As such we hypothesized that it might be possible to detect rhinovirus (RV), the virus most frequently implicated in acute asthma, in lung tissue from patients who died from asthma. Methodology: We studied archival, wax-embedded lung tissue obtained postmortem from: (i) patients who died from asthma (n = 12), (ii) asthma patients with non-asthma-related death (n = 3), and (iii) non-asthmatic individuals who died from unrelated causes (n = 3). A validated reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect RV. To confirm RNA preservation, RT-PCR was used to detect expression of the constitutive gene adenine-phosphoribosyl-transferase (APRT). Sensitivity of the assay was assessed using wax-embedded RV-infected cells. Results: Sensitivity of RT-PCR for RV in wax-embedded sections was similar to previous studies (approximately 100 viral copies). Specimens used for study were predominantly of alveolar and small airway origin (< 2 mm). All tissues examined were negative for the presence of RV mRNA and positive for APRT mRNA. Conclusions: RV infection of the lower airway may be an uncommon cause of fatal asthma. Alternatively, RV may not extend to peripheral airways and more proximal tissue sampling or PCR assays for other viruses may be required to determine an association between viral respiratory tract infection and fatal asthma. [source] Allografts Stimulate Cross-Reactive Virus-Specific Memory CD8 T Cells with Private SpecificityAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010M. A. Brehm Viral infections have been associated with the rejection of transplanted allografts in humans and mice, and the induction of tolerance to allogeneic tissues in mice is abrogated by an ongoing viral infection and inhibited in virus-immune mice. One proposed mechanism for this ,heterologous immunity' is the induction of alloreactive T cell responses that cross-react with virus-derived antigens. These cross-reactive CD8 T cells are generated during acute viral infection and survive into memory, but their ability to partake in the immune response to allografts in vivo is not known. We show here that cross-reactive, virus-specific memory CD8 T cells from mice infected with LCMV proliferated in response to allografts. CD8 T cells specific to several LCMV epitopes proliferated in response to alloantigens, with the magnitude and hierarchy of epitope-specific responses varying with the private specificities of the host memory T cell repertoire, as shown by adoptive transfer studies. Last, we show that purified LCMV-specific CD8 T cells rejected skin allografts in SCID mice. These findings therefore implicate a potential role for heterologous immunity in virus-induced allograft rejection. [source] Viral Infection Induces De Novo Lesions of Coronary Allograft Vasculopathy Through a Natural Killer Cell-Dependent PathwayAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009J. A. Graham Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG,/,). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes. [source] Therapy of other viral infections: herpes to hepatitisDERMATOLOGIC THERAPY, Issue 6 2004Arun Chakrabarty ABSTRACT:, Over the past several years, there has been an increase in knowledge pertaining to the diagnosis and management strategies for the herpes family (Types 1,8), the pox viruses, mumps, measles, rubella, and parvovirus B19 as well as the viral etiologies of hepatitis. Various antiviral treatments, such as nucleoside analogs and interferon therapy, have been available to reduce the signs and symptoms of these common viral infections. This article summarizes the preferred treatment strategies to be employed for each of the viruses for reducing severity, duration, recurrences (notably in the herpes family), transmission rates, as well as preventive alternatives. The majority of the therapeutic options attenuate the course of disease. Treatment decisions are driven by knowledge of the natural history and often are tailored to incorporate clinical circumstances for individual patients. Promotion of community awareness and the development of vaccines should be emphasized in the battle against these common viruses, particularly the herpes simplex viruses, the pox viruses, and hepatitis B. [source] Viral infections as potential triggers of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2007Nienke van der Werf Abstract During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct ,-cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes-susceptible individuals in order to delay or even prevent the diabetogenic process. Copyright © 2007 John Wiley & Sons, Ltd. [source] Association between lymphocyte proliferation and polychlorinated biphenyls in free-ranging harbor seal (Phoca vitulina) pups from British Columbia, CanadaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2005Milton Levin Abstract Recent pinniped die-offs have led to the speculation that persistent organic pollutants (POPs) are immunomodulatory, making individuals more susceptible to viral infections. Eighteen healthy harbor seal (Phoca vitulina) pups (aged 3,4 weeks) were live-captured from southern British Columbia, Canada, and maintained temporarily in captivity for an immunotoxicological assessment. The relationships between mitogen-induced peripheral blood lymphocyte proliferation and blubber concentrations of three major immunotoxic POP classes (the polychlorinated biphenyls [PCBs], polychlorinated dibenzo- p -dioxins [PCDDs], and the polychlorinated dibenzofurans [PCDFs]) were evaluated. A significant body weight-independent positive correlation was observed between both T-cell mitogen (phytohemagglutinin [PHA])- and B-cell mitogen (lipopolysaccharide [LPS])-induced lymphocyte proliferation and the blubber concentrations of total PCB. Best subset regression analysis revealed that total PCBs, and not total PCDD or total PCDF, explained 24 and 29% of the changes in both T-cell mitogen-and B-cell mitogen-induced lymphocyte proliferation, respectively. Further regression analysis performed on the PCB classes measured in this study showed that di - ortho PCBs accounted for 25 and 30% of the changes in both T-cell and B-cell lymphocyte proliferation, respectively. Results suggest that POPs, and PCBs in particular, are associated with changes in lymphocyte proliferation, something that could result in increased susceptibility to infections in harbor seal pups. Further research is needed to evaluate the relative roles of natural and contaminant-related influences on the immune system of marine mammals. [source] Inflammatory airway disease, nasal discharge and respiratory infections in young British racehorsesEQUINE VETERINARY JOURNAL, Issue 3 2005J. L. N. WOOD Summary Reasons for performing study: Respiratory disease is important in young Thoroughbred racehorses, but the variation in the rates of occurrence between different ages and training groups has not been characterised. Objectives: To determine the rates of respiratory disease, particularly inflammatory airway disease (IAD), as well as evidence of infection, and their variation between age and group. Methods: Horses were examined monthly in 7 British flat training yards over a 3 year period. IAD was defined as increased mucus in the trachea with increased proportions of neutrophils in tracheal wash samples. Frequencies of disease outcomes were estimated from the data. Results: The prevalence of IAD was 13.8% and the incidence was 8.9 cases/100 horses/month. Rates varied with training and age groups, decreasing in older animals. The prevalence of nasal discharge (ND) was 4.1%. Rates of bacterial isolation were more common than viral infections. The incidence and prevalence of several bacterial species decreased with age. Conclusions: IAD and ND were common in young racehorses, varying significantly between training groups and decreasing with age, consistent with infection playing a role in aetiology. Potential relevance: The high prevalence of IAD in 2-year-old horses in Britain suggests that routine endoscopic examination may be helpful in providing early diagnosis and appropriate therapy. The transmission of bacteria and viruses within and between groups of young animals and the role of infection, stable environment and factors inherent to each horse, including their genetic make-up, in the multifactorial aetiology of the disease all merit further study. [source] A case of immune recovery vitritis induced by donor leukocyte infusion for the treatment of cytomegalovirus retinitisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Manabu Kawakami Abstract:, Donor leukocyte infusion (DLI) has been successfully used for some life-threatening viral infections after stem cell transplantation (SCT). We describe here the first case of DLI treatment for cytomegalovirus (CMV) retinitis. A 49-year-old female patient with AML, M1 underwent SCT with a reduced-intensity conditioning regimen from HLA-haploidentical son. On day +140, the patient developed CMV retinitis of her left eye despite the continuing antiviral therapy. DLI at a dose of 1 × 105 CD3+ cells/kg was added to ganciclovir and foscarnet therapy. Eighteen days after the DLI, the funduscopic findings revealed improvement of the retinitis and the development of vitreous inflammation. Simultaneously, the number of CD4+ cells in the peripheral blood rapidly increased. Thus, we consider it likely that DLI induced a local immune response against CMV antigens, which resulted in the immune recovery vitritis. This case suggested the potentiality of DLI for the treatment of CMV retinitis. [source] Interleukin-4 downregulates CD127 expression and activity on human thymocytes and mature CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2010Angela M. Crawley Abstract Signaling via the IL-7 receptor complex (IL-7R,/CD127 and IL-2R,/CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2R,-sharing (,C) cytokines decrease CD127 expression on CD4+ and CD8+ T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8+ T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naïve (CD45RA+) CD8+ T cells, without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8+ T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8+ T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8+ T cells, IL-4 is a potential contributor to impaired CD8+ T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated. [source] Here today , not gone tomorrow: Roles for activating receptors in sustaining NK cells during viral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010Seung-Hwan Lee Abstract The conclusive evidence supporting a role for NK cells in defense against viruses has been obtained under conditions of NK cell deficiencies prior to infections. NK cell proliferation can be induced during infections, but the advantages of resulting expansion have been unclear because NK cell basal frequency is already high. However, NK cell decreases are also observed during certain conditions of viral infection. Given the range of potent antiviral and immunoregulatory functions of NK cells, such "disappearance" dramatically changes the resources available to the host. New studies demonstrate that proliferation dependent on activating receptors for virus-induced ligands is key for NK cell maintenance, and allows their continued availability for control of adaptive immune responses and immunopathology. This pathway for sustaining NK cells may represent a system used generally to select subsets for rescue during homeostatic purging. In the case of NK cells, though, nonselection limits continued access to the many beneficial functions of NK cells. The observations resolve the long-standing conundrum of reported NK cell increases and decreases during viral infections. Moreover, they demonstrate a previously unappreciated role for activating receptors, i.e. to keep NK cells here today and also tomorrow. [source] CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2009Niall D. MacHugh Abstract Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor , chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection. [source] CTL quality and the control of human retroviral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Charles R. M. Bangham Abstract The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or "quality" at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects , or both , of the variation in the efficiency of virus control. [source] Effector T-cell differentiation during viral and bacterial infections: Role of direct IL-12 signals for cell fate decision of CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Selina J. Keppler Abstract To study the role of IL-12 as a third signal for T-cell activation and differentiation in vivo, direct IL-12 signaling to CD8+ T cells was analyzed in bacterial and viral infections using the P14 T-cell adoptive transfer model with CD8+ T cells that lack the IL-12 receptor. Results indicate that CD8+ T cells deficient in IL-12 signaling were impaired in clonal expansion after Listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or vesicular stomatitis virus. Although limited in clonal expansion after Listeria infection, CD8+ T cells deficient in IL-12 signaling exhibited normal degranulation activity, cytolytic functions, and secretion of IFN-, and TNF-,. However, CD8+ T cells lacking IL-12 signaling failed to up-regulate KLRG1 and to down-regulate CD127 in the context of Listeria but not viral infections. Thus, direct IL-12 signaling to CD8+ T cells determines the cell fate decision between short-lived effector cells and memory precursor effector cells, which is dependent on pathogen-induced local cytokine milieu. [source] Development of human plasmacytoid dendritic cells depends on the combined action of the basic helix-loop-helix factor E2-2 and the Ets factor Spi-B,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008Maho Nagasawa Abstract Plasmacytoid dendritic cells (pDC) are central players in the innate and adaptive immune response against viral infections. The molecular mechanism that underlies pDC development from progenitor cells is only beginning to be elucidated. Previously, we reported that the Ets factor Spi-B and the inhibitors of DNA binding protein 2 (Id2) or Id3, which antagonize E-protein activity, are crucially involved in promoting or impairing pDC development, respectively. Here we show that the basic helix-loop-helix protein E2-2 is predominantly expressed in pDC, but not in their progenitor cells or conventional DC. Forced expression of E2-2 in progenitor cells stimulated pDC development. Conversely, inhibition of E2-2 expression by RNA interference impaired the generation of pDC suggesting a key role of E2-2 in development of these cells. Notably, Spi-B was unable to overcome the Id2 enforced block in pDC development and moreover Spi-B transduced pDC expressed reduced Id2 levels. This might indicate that Spi-B contributes to pDC development by promoting E2-2 activity. Consistent with notion, simultaneous overexpression of E2-2 and Spi-B in progenitor cells further stimulated pDC development. Together our results provide additional insight into the transcriptional network controlling pDC development as evidenced by the joint venture of E2-2 and Spi-B. [source] Influenza A virus abrogates IFN-, response in respiratory epithelial cells by disruption of the Jak/Stat pathwayEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Kohsaku Uetani Abstract The innate immunity to viral infections induces a potent antiviral response mediated by interferons (IFN). Although IFN-, is detected during the acute stages of illness in the upper respiratory tract secretions and in the serum of influenza A virus-infected individuals, control of influenza A virus is not dependent upon IFN-, as evidenced by studies using anti-IFN-, Ab and IFN-,,/, mice. Thus, we hypothesized that IFN-, is not critical in host survival because influenza A virus has mechanisms to evade the antiviral activity of IFN-,. To test this, A549 cells, an epithelial cell line derived from lung adenocarcinoma, were infected with influenza virus strain A/Aichi/2/68 (H3N2) (Aichi) and/or stimulated with IFN-, to detect IFN-,-stimulated MHC class II expression. Influenza A virus infection inhibited IFN-,-induced up-regulation of HLA-DR, mRNA and the IFN-, induction of class II transactivator (CIITA), an obligate mediator of MHC class II expression. Nuclear translocation of Stat1, upon IFN-, stimulation was significantly inhibited in influenza A virus-infected cells and this was associated with a decrease in Tyr701 and Ser727 phosphorylation of Stat1,. Thus, influenza A virus subverts antiviral host defense mediated by IFN-, through effects on the intracellular signaling pathways. [source] IL-2 induces in vivo suppression by CD4+CD25+Foxp3+ regulatory T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2008Susan Brandenburg Abstract Interleukin-2 (IL-2) treatment is currently used to enhance T cell-mediated immune responses against tumors or in viral infections. At the same time, IL-2 is essential for the peripheral homeostasis of CD4+CD25+Foxp3+ regulatory T cells (Treg). In our study, we show that IL-2 is also an important activator of Treg suppressive activity in vivo. IL-2 treatment induces Treg expansion as well as IL-10 production and increases their suppressive potential in vitro. Importantly, in vivo application of IL-2 via gene-gun vaccination using IL-2 encoding DNA plasmids (pIL-2) inhibited naive antigen-specific T cell proliferation as well as a Th1-induced delayed type hypersensitivity response. The suppressive effect can be transferred onto naive animals by Treg from IL-2-treated mice and the suppression depends on the synergistic action of IL-10 and TGF-,. These data highlight that during therapeutic treatment with IL-2 the concomitant activation of Treg may indeed counteract the intended activation of cellular immunity. [source] Mediastinal lymph node CD8,, DC initiate antigen presentation following intranasal coadministration of ,-GalCerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Sung-Youl Ko Abstract Our previous study revealed that ,-galactosylceramide (,-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and ,-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and ,-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8,,B220,CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8,,B220,CD11c+ DC subset than those of other DC subsets. These results indicate that CD8,,B220,CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when ,-GalCer is coadministered as a nasal vaccine adjuvant. [source] Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2007Martin Abstract IL-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro T cell proliferation but is also essential for down-regulating T cell responses by inducing activation-induced cell death as well as regulatory T cells. The in vivo analysis of IL-2 function in regulating specific T cell responses has been hampered by the fact that mice deficient in IL-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. Here we generated chimeric mice harboring both IL-2R-competent and IL-2R-deficient T cells and assessed CD8+ T cell induction, function and maintenance after acute or persistent viral infections. Induction and maintenance of CD8+ T cells were relatively independent of IL-2R signaling during acute/resolved viral infection. In marked contrast, IL-2 was crucial for secondary expansion of memory CD8+ T cells and for the maintenance of virus-specific CD8+ T cells during persistent viral infections. Thus, depending on the chronicity of antigen exposure, IL-2R signaling is either essential or largely dispensable for induction and maintenance of virus-specific CD8+ T cell responses. [source] Bone marrow-derived cells expand memory CD8+ T,cells in response to viral infections of the lung and skinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Gabrielle Abstract While naive CD8+ T,cells have been shown to require bone marrow-derived dendritic cells (DC) to initiate immunity, such a requirement for memory CD8+ T,cells has had limited assessment. By generating bone marrow chimeras that express the appropriate antigen-presenting molecules on either radiation-sensitive bone marrow-derived or radiation-resistant non-bone marrow-derived compartments, we showed that both primary and secondary immune responses to influenza virus infection of the lung were initiated in the draining LN. This required cells of bone marrow origin, most likely DC, for optimal expansion within the secondary lymphoid compartment. This was similarly the case with HSV-1 infection of the skin. As Langerhans cells are radioresistant, unlike other DC populations, these studies also demonstrate that the radiosensitive DC responsible for secondary expansion of HSV-specific memory are not Langerhans cells. [source] Immune response modifiers , mode of actionEXPERIMENTAL DERMATOLOGY, Issue 5 2006Meinhard Schiller Abstract:, The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-,B activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-,, and production of type I IFNs (IFN-, and IFN-,), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response. [source] Dengue virus-specific suppressor T cells: current perspectivesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2007Umesh C. Chaturvedi Abstract Dengue virus was the first microorganism that was shown to induce generation of antigen-specific suppressor T (TS) cells in mice. The cascade of the three generations of TS cells (TS1, TS2, TS3) and their secretary products, the suppressor factors (SF1, SF2), was delineated. The TS pathway was proposed to be protective through inhibition of the production of enhancing antibody, which may enhance the severity of dengue disease. The currently second most favoured mechanism of severe dengue disease is the ,cytokine tsunami'. During the last decade, suppressor/regulatory T cells have been studied in greater detail using modern techniques in various diseases, including viral infections. This brief review discusses the role of dengue-specific suppressor T cells in protection and/or induction of severe dengue disease in view of our current understanding of suppressor/regulatory T cells. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||