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Cellular Immunity (cellular + immunity)
Selected AbstractsIn-vitro Fertilization and Embryo Transfer and Cellular Immunity: Study on Cytokines and T Lymphocyte subpopulations in IVF-ET CyclesJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2002Mitsutaka Murakami Objectives: To determine whether peripheral T lymphocyte subpopulations and cytokines change during in-vitro fertilization and embryo transfer (IVF-ET) cycles and to evaluate them with regard to pregnancy status and types of infertility. Methods: Peripheral T lymphocyte subpopulations and cytokines in 33 consecutive cycles of IVF-ET were examined. All the women were stimulated with purified FSH and hCG after pituitary suppression with GnRH agonist. Peripheral blood samples were collected before FSH administration, on the day of hCG administration, the day of ET (day 2), day 6 and day 15. We measured plasma estradiol and progesterone levels and plasma interferon-,, interleukin-4 (IL-4), IL-10 and IL-12 levels. Peripheral T lymphocyte subpopulations, T helper type 1 and 2 cells (Th1 and Th2) and T cytotoxic type 1 and 2 cells (Tc1 and Tc2), were analyzed with three-color flowcytometry. Results: There were no changes in the plasma levels of the cytokines or in the proportions of Th1 and Th2 and the proportions of Tc1 and Tc2 in peripheral blood lymphocytes during the IVF-ET cycles. In women with endometriosis, the ratios of Tc1 to CD8+ lymphocytes and the Tc1 to Tc2 ratios before FSH administration were much higher than in women without endometriosis. The ratios of Tc1 to CD8+ lymphocytes were significantly lower in the patients with endometriosis who became pregnant. Conclusions: Peripheral cellular immunity does not change during IVF-ET cycles. In women with endometriosis, the peripheral Tc1 subpopulation is more predominant before ovarian stimulation, suggest- ing that the ratio of Tc1 before ovarian stimulation could be an indicator of fecundity for women with endometriosis. [source] Physiological functions of hemocytes newly emerged from the cultured hematopoietic organs in the silkworm, Bombyx moriINSECT SCIENCE, Issue 1 2010Cheng-Long Wang Abstract, Cellular immunity is a very important part of insect innate immunity. It is not clear if hemocytes entering the hemolymph require a maturation process to become competent. The establishment of a tissue culture system for the insect hematopoietic organs would enable physiological function assays with hemocytes newly emerged from hematopoietic organs. To this end, we established a hematopoietic organ culture system for the purebred silkworm pnd pS and then studied the physiological functions of the newly emerged hemocytes. We found that Grace's medium supplemented with 10% heated silkworm larval plasma was better for culturing the hematopoietic organs of pnd pS. Newly emerged hemocytes phagocytosed propidium iodide-labeled bacteria and encapsulated the Iml-2 coated nickel beads as well as pupal tissue debris. This culture system is therefore capable of generating physiologically functional hemocytes. These hemocytes can be used to study the mechanisms of the hemocyte immune response among others. [source] Cellular immunity in Wegener's granulomatosis: Characterizing T lymphocytesARTHRITIS & RHEUMATISM, Issue 6 2009Annelies E. Berden First page of article [source] Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infectionCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2008D. Hegazy Summary Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed,uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27·6% of exposed,uninfected cases compared with 16·7% of healthy controls [,2 = 6·3, P = 0·02, odds ratio (OR) = 1·9, 95% confidence interval (CI) = 1·1,3·2]. CC genotype was found in 10·5% of exposed,uninfected cases compared with 0·9% controls (,2 = 9·3, P = 0·01, OR = 12, 95% CI = 1·5,100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed,uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection. [source] Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+ cellsDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2006Hagit Cohen Abstract Peripheral cellular immunity was recently shown to play a critical role in brain plasticity and performance. The antigenic specificity of the participating T cells, however, was not investigated, and nor was their relevance to psychological stress. Here we show, using a mouse model, that adaptive immunity mitigates maladaptation to the acute psychological stress known to trigger abnormal behaviors reminiscent of human post-traumatic stress disorder. Assessment of behavioral adaptation (measured by the acoustic startle response and avoidance behavior) in mice after their exposure to predator odor revealed that maladaptation was several times more prevalent in T cell-deficient mice than in their wild-type counterparts. A single population of T cells reactive to central nervous system (CNS)-associated self-protein was sufficient to endow immune-deficient mice with the ability to withstand the psychological stress. Naturally occurring CD4+CD25+ regulatory T cells were found to suppress this endogenous anti-stress attribute. These findings suggest that T cells specific to abundantly expressed CNS antigens are responsible for brain tissue homeostasis and help the individual to cope with stressful life episodes. They might also point the way to development of immune-based therapies for mental disorders, based either on up-regulation of T cells that partially cross-react with self-antigens or on weakening of the activity of regulatory T cells. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Temperature and Ca2+ ion as modulators in cellular immunity of the Sunn pest Eurygaster integriceps Puton (Heteroptera: Scutelleridae)ENTOMOLOGICAL RESEARCH, Issue 6 2009Arash ZIBAEE Abstract Environmental conditions in addition to divalent cations may affect the interactions between pathogens and insects. Elucidation of factors which modulate insect immune responses could be a significant part of investigations in this area. In this study, adults of Eurygaster integriceps, as the destructive pest of wheat, were kept at different temperatures in addition to injection with different concentrations of Ca2+ to find the effect on cellular immune reactions against Beauveria bassiana. Results showed that total and differentiate hemocyte numbers, nodule formation and phenoloxidase activity increased with elevation of temperature so that the higher values were obtained at 30 and 40°C at various intervals. Higher concentrations of Ca2+ ion (5 mM) caused an increase in plasmatocyte length and width especially after 60 min. Similar results were observed for nodule formation and phenoloxidase activity of E. integriceps adults after injection by B. bassiana spores and phenoloxidase activity. It is clear from the current study that thermoregulation and Ca2+ ion can positively affect the hemocyte numbers especially plasmatocytes and granulocytes, nodule formation and phenoloxidase activity in E. integriceps. The understanding of modulators of the insect immune response may directly influence novel approaches to obtain safe and effective biological control agents. [source] Post-surgical irradiation causes cellular immune suppression in patients with breast cancerEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2009G.V. KOUKOURAKIS md According to several studies, even the locoregional irradiation of patients with carcinoma can cause a severe and rather alarming cellular immune defect. We thus designed a prospective research in order to study the effect of post-operative irradiation on cellular immunity in patients suffering from breast cancer. In 35 patients with breast cancer who required post-operative irradiation, four blood samples were taken at indicated point times. Nineteen out of 35 patients received post-surgical chemotherapy before irradiation. The total lymphocytes as well as CD4 and CD8 subpopulations were measured by using flow cytometry analysis. The mean T-lymphocyte (Tol) count dropped from 1487.77 to 1227.91 (P = 0.0013) and the CD4+ count from 674.17 to 580.91 (P = 0.0189). The mean value of CD8+ dropped from 421.31 to 314.00 (P = 0.0003). Moreover, a statistically significant difference regarding the pattern of temporal change was observed between a group of patients that received irradiation only and a group that received radiation therapy (RT) with chemotherapy (P -values 0.0015, 0.01 and 0.092 for Tol, CD4+ and CD8+ respectively). The group of patients that received RT only presented a more rapid decrease of Tol concerning the decrease observed in the group that underwent chemotherapy and RT. [source] Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitroEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007K. Hoetzenecker Abstract Background Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. Materials and methods/results CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFN,), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and Fc,RIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. Conclusions We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response. [source] Interferon-, in healthy subjects: selective modulation of inflammatory mediatorsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2001J. De Metz Background It is suggested that interferon-, (IFN-,), like other cytokines, is a mediator in the host inflammatory response, which could be of importance in the pathophysiology of sepsis. The role of IFN-, in human host inflammatory responses, however, has not been studied. Design In a placebo-controlled trial we studied the acute effects of IFN-, administration on host inflammatory mediators in healthy men: i.e. the cytokine/chemokine cascade system, acute-phase proteins, activation markers of the innate cellular immunity and coagulation/fibrinolysis parameters. Results IFN-, increased plasma levels of interleukin-6 (IL-6), IL-8 and IFN-,-inducible protein-10 (IP-10) (P < 0·05), but did not affect plasma levels of other cytokines (IL-4, IL-10, tumour necrosis factor-,, IL-12p40/p70). Plasma concentrations of C-reactive protein and secretory phospholipase A2 both increased (P < 0·05). Plasma levels of the leucocyte activation marker elastase-,1,antitrypsin complexes increased after IFN-, administration (P < 0·05), IFN-, increased the percentage of high-affinity Fc,-receptor (Fc,RI) -positive neutrophils (P < 0·05), but did not affect the mean fluorescence intensity of Fc,RI on neutrophils. Procoagulant and profibrinolytic effects of IFN-, were evidenced by increased plasma levels of prothrombin fragment F1 + F2, tissue-plasminogen activator and plasmin-,2,antiplasmin complexes (P < 0·05). Conclusion We conclude that IFN-, selectively affects host inflammatory mediators in humans. [source] Targeting of LcrV virulence protein from Yersinia pestis to dendritic cells protects mice against pneumonic plagueEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010Yoonkyung Do Abstract To help design needed new vaccines for pneumonic plague, we targeted the Yersinia pestis LcrV protein directly to CD8,+ DEC-205+ or CD8,, DCIR2+ DC along with a clinically feasible adjuvant, poly IC. By studying Y. pestis in mice, we could evaluate the capacity of this targeting approach to protect against a human pathogen. The DEC-targeted LcrV induced polarized Th1 immunity, whereas DCIR2-targeted LcrV induced fewer CD4+ T cells secreting IFN-,, but higher IL-4, IL-5, IL-10, and IL-13 production. DCIR-2 targeting elicited higher anti-LcrV Ab titers than DEC targeting, which were comparable to a protein vaccine given in alhydrogel adjuvant, but the latter did not induce detectable T-cell immunity. When DEC- and DCIR2-targeted and F1-V+ alhydrogel-vaccinated mice were challenged 6,wk after vaccination with the virulent CO92 Y. pestis, the protection level and Ab titers induced by DCIR2 targeting were similar to those induced by F1-V protein with alhydrogel vaccination. Therefore, LcrV targeting to DC elicits combined humoral and cellular immunity, and for the first time with this approach, also induces protection in a mouse model for a human pathogen. [source] How B cells shape the immune response against Mycobacterium tuberculosisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2009Paul J. Maglione Abstract Extensive work illustrating the importance of cellular immune mechanisms for protection against Mycobacterium tuberculosis has largely relegated B-cell biology to an afterthought within the tuberculosis (TB) field. However, recent studies have illustrated that B lymphocytes, through a variety of interactions with the cellular immune response, play previously underappreciated roles in shaping host defense against non-viral intracellular pathogens, including M. tuberculosis. Work in our laboratory has recently shown that, by considering these lymphocytes more broadly within their variety of interactions with cellular immunity, B cells have a significant impact on the outcome of airborne challenge with M. tuberculosis as well as the resultant inflammatory response. In this review, we advocate for a revised view of TB immunology in which roles of cellular and humoral immunity are not mutually exclusive. In the context of our current understanding of host defense against non-viral intracellular infections, we review recent data supporting a more significant role of B cells during M. tuberculosis infection than previously thought. [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] Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2008Yoonkyung Do Abstract There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205/CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC-205+ DC in situ. We observed antigen-specific CD4+ T cell immunity measured by intracellular staining for IFN-, in three different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not observe such T cell responses with F1-V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4+ T cell mimetopes in each MHC haplotype, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly increased the efficiency for inducing IFN-,-producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1-V subunit vaccine, but Th1-dependent IgG2a and IgG2c isotypes were observed only after anti-DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-,-producing T cells in Y.,pestis infection. [source] Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class,I invariant regionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Linda Wooldridge Abstract CD8+ cytotoxic T,lymphocytes (CTL) are key determinants of immunity to intracellular pathogens and neoplastic cells. Recognition of specific antigens in the form of peptide-MHC class,I complexes (pMHCI) presented on the target cell surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds to invariant domains of pMHCI and facilitates antigen recognition. Here, we investigate the biological effects of a Q115E substitution in the ,2,domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by,,50% without altering TCR/pMHCI interactions. Soluble and cell surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL without loss of specificity. These CD8-enhanced antigens induce greater CD3 ,,chain phosphorylation in cognate CTL leading to substantial increases in cytokine production, proliferation and priming of naive T cells. This effect provides a fundamental new mechanism with which to enhance cellular immunity to specific T cell antigens. [source] Anti-tumor MHC class,Ia-unrestricted CD8 T,cell cytotoxicity elicited by the heat shock protein gp96EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2004Ana Goyos Abstract In Xenopus as in mammals, gp96 stimulates MHC-restricted cellular immunity against chaperoned minor histocompatibility (H) antigens (Ag). In adult Xenopus, gp96 also elicits peptide-specific effectors against MHC class,Ia-negative 15/0 tumors. To determine whether gp96 can generate functionally heterogeneous CD8+ effectors (CTL that kill MHC class,Ia+ minor,H-Ag-disparate lymphoblasts and MHC class,Ia, tumor targets), LG-6 isogenetic frogs were immunized with gp96 purified either from MHC-identical but minor,H-Ag-disparate LG-15 normal tissues or from the MHC class,Ia-negative 15/0 tumor line (derived from LG-15 frogs). LG-15 normal liver-derived gp96 did not induce detectable CD8+in vitro killing against 15/0 tumor cells. However, 15/0-derived gp96 did induce killing against both MHC class,Ia+ LG-15 lymphoblasts and the MHC class,Ia, 15/0 tumor, but not against another MHC class,Ia, tumor (B3B7) or against LG-6 lymphoblasts. Tumor killing was better when 15/0 rather than normal LG-15 irradiated stimulators were used, but in vitro stimulation without prior in vivo immunization was ineffective. These data suggest that (1),15/0-derived gp96 chaperones minor,H-Ag shared with normal LG-15 lymphocytes and elicits MHC-restricted CTL, and (2),15/0-derived gp96, but not normal liver-derived gp96, generates CD8+ effectors that kill 15/0 tumor cells in the absence of MHC class,Ia expression. [source] Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Joseph M. Bliss Abstract This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans -specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell,cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections. [source] Antibody bound to the surface antigen MPB83 of Mycobacterium bovis enhances survival against high dose and low dose challengeFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2004Mark A. Chambers Abstract Tuberculosis caused by infection with Mycobacterium tuberculosis or Mycobacterium bovis is a significant disease of man and animals. Whilst cellular immunity is the major immunological component required for protection against these organisms, recent reports have suggested that monoclonal antibodies can modify infection with M. tuberculosis. To test whether the same was true for M. bovis infection, we determined the effect of preincubation of M. bovis with a monoclonal antibody on subsequent intravenous infection of mice. Antibodies bound to the surface of M. bovis increased the survival time of mice infected with M. bovis and changed the morphology of granulomas and the distribution of acid-fast bacilli in the lung. These studies suggest that antibodies directed to the surface of virulent mycobacteria can modulate their virulence in vivo. [source] Selective expression of inhibitory Fc, receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular responseINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Lydie Cassard Abstract During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (Fc,R) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the Fc,RIIB1, an inhibitory isoform of Fc,R. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of Fc,RIIB is restricted to melanoma and is acquired during tumor progression. We show that Fc,RIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of Fc,RIIB. Using experimental mouse models, we demonstrate that expression of Fc,RIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify Fc,RIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to Fc,R-dependent innate effector responses. © 2008 Wiley-Liss, Inc. [source] Dendritic cell vaccination and immune monitoringISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2009E. H. J. G. Aarntzen Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. Following infection or inflammation, they undergo a complex process of maturation and migrate to lymph nodes where they present antigens to T cells. Their decisive role in inducing immunity formed the rationale for DC immunotherapy: DCs loaded with tumour antigens are injected into cancer patients to stimulate T cells to eradicate tumours. Effective immune responses and favourable clinical outcomes have indeed been observed, but only in a minority of patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof-of-principle trials the fate, interactions and effectiveness of the injected DC. The success of DC-based immunotherapy to induce cellular immunity against tumours is highly dependent on accurate delivery and trafficking of the DC to T cell-rich areas of secondary lymphoid tissues. [source] Daytime variation in T-cell-mediated immunity of Eurasian kestrel Falco tinnunculus nestlingsJOURNAL OF AVIAN BIOLOGY, Issue 5 2006Jesús Martínez-PadillaArticle first published online: 15 AUG 200 Host-parasite interactions are central in evolutionary and behavioural ecology. In the last few years, skin injections of the mitogen Phytohaemagglutinin (PHA) have become one of the most important and widely used in-vivo assays of immune function in birds. However, there are no studies of the circadian variation suggesting that care should be taken interpreting results when using this technique. This 3-year study assessed PHA responses as a function of daylight time in 310 Eurasian kestrel Falco tinnunculus nestlings at 24 days of age in Central Spain. I found that T-cell-mediated immunity was positively related to nestling mass and varied among years. Controlling for these variables, I also found that T-cell-mediated immunity decreased with the hour of sampling, and that this pattern was consistent between years. In addition, I found that at the end of the day only, T-cell-mediated immunity decreased with brood size. Parasites seem not to be behind this pattern, but I suggest that the cumulative effect of sibling competition during the day might explain the decrease of cellular immunity with the hour of sampling. Thus, I strongly recommend that future studies of cellular immunity should control for this potential source of variation when nestling self-maintenance is evaluated by the PHA-induced skin-swelling response. [source] A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificitiesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Maurizio Provenzano Abstract Human cytomegalovirus (HCMV) can cause life-threatening disease in infected hosts. Immunization with human leukocyte antigen (HLA)-restricted immunodominant synthetic peptides and adoptive transfer of epitope-specific T cells have been envisaged to generate or boost HCMV-specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65-derived peptide (pp65340,355, RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4+ and CD8+ T cells, restricted by a wide range of HLA class I and II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4+ T cells, including proliferation, killing of autologous HCMV-infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4+ and CD8+ T-cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation. [source] Effects of peripheral benzodiazepine receptor ligands on proliferation and differentiation of human mesenchymal stem cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004D.H. Lee The peripheral benzodiazepine receptor (PBR) has been known to have many functions such as a role in cell proliferation, cell differentiation, steroidogenesis, calcium flow, cellular respiration, cellular immunity, malignancy, and apoptosis. However, the presence of PBR has not been examined in mesenchymal stem cells. In this study, we demonstrated the expression of PBR in human bone marrow stromal cells (hBMSCs) and human adipose stromal cells (hATSCs) by RT-PCR and immunocytochemistry. To determine the roles of PBR in cellular functions of human mesenchymal stem cells (hMSCs), effects of diazepam, PK11195, and Ro5-4864 were examined. Adipose differentiation of hMSCs was decreased by high concentration of PBR ligands (50 ,M), whereas it was increased by low concentrations of PBR ligands (<10 ,M). PBR ligands showed a biphasic effect on glycerol-3-phosphate dehydrogenase (GPDH) activity. High concentration of PBR ligands (from 25 to 75 ,M) inhibited proliferation of hMSCs. However, clonazepam, which does not have an affinity to PBR, did not affect adipose differentiation and proliferation of hMSCs. The PBR ligands did not induce cell death in hMSCs. PK11195 (50 ,M) and Ro5-5864 (50 ,M) induced cell cycle arrest in the G2/M phase. These results indicate that PBR ligands play roles in adipose differentiation and proliferation of hMSCs. J. Cell. Physiol. 198: 91,99, 2004. © 2003 Wiley-Liss, Inc. [source] Carotenoid and protein supplementation have differential effects on pheasant ornamentation and immunityJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2007H. G. SMITH Abstract A currently popular hypothesis states that the expression of carotenoid-dependent sexual ornaments and immune function may be correlated because both traits are positively affected by carotenoids. However, such a correlation may arise for another reason: it is well known that immune function is dependent on nutritional condition. A recent study has suggested that the expression of ornaments may too depend on nutritional condition, as males in good nutritional condition are better at assimilating and/or modulating carotenoids. Thus, carotenoid-dependent ornaments and immune function may be correlated because both are dependent on nutritional condition. To elucidate if, and how, ornamentation and immune function are linked, pheasant diets were supplemented with carotenoid and/or protein in a fully factorial experiment. Carotenoid treatment affected wattle coloration and tail growth, but not cellular or humoral immunity. Immunity was unrelated to males' initial ornamentation including wattle colour. Males in better body condition, measured as residual mass, increased their wattle coloration more when carotenoid supplemented. Protein positively affected humoral but not cellular immunity, but had no effect on ornaments. Cellular, but not humoral, immunity increased with male body condition. Thus, there was no evidence that an immune-stimulatory effect of carotenoids resulted in wattle coloration honestly signalling immune function, but wattle coloration may still signal male body condition. [source] Maternal circulating interferon-, and interleukin-6 as biomarkers of Th1/Th2 immune status throughout pregnancyJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008Aziz Aris Abstract Aim:, T cells may be classified as T helper type 1 (Th1) cells, which synthesize cytokines inducing cellular immunity, or T helper type 2 (Th2), which synthesize cytokines inducing humoral immunity. According to the Th1/Th2 paradigm, it has been postulated that successful pregnancy induces an immune Th2 bias, but it is not yet clear how Th1 and Th2 systems vary simultaneously throughout the pregnancy. Methods:, Using maternal circulating interferon-, (IFN-,) and interleukin-6 (IL-6) as biomarkers of Th1 and Th2 cytokines, respectively, we examined the variation of circulating Th1/Th2 ratio in 35 healthy pregnant women from 10 to 40 weeks of pregnancy. Results:, With increasing gestational age, maternal circulating levels of IFN-, decrease, whereas those of IL-6 increase. The IFN-,/IL-6 ratio switches around the 19th week of pregnancy. Conclusions:, Our results suggest that maternal systemic IFN-, and IL-6 concentrations may be biomarkers of Th1/Th2 immune status during pregnancy. Moreover, our findings showed that contrary to the Th1/Th2 paradigm, the Th1 bias may be prevailing at the beginning of pregnancy, balanced in the middle of pregnancy and supplanted by the Th2 bias at the end of pregnancy. [source] In-vitro Fertilization and Embryo Transfer and Cellular Immunity: Study on Cytokines and T Lymphocyte subpopulations in IVF-ET CyclesJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2002Mitsutaka Murakami Objectives: To determine whether peripheral T lymphocyte subpopulations and cytokines change during in-vitro fertilization and embryo transfer (IVF-ET) cycles and to evaluate them with regard to pregnancy status and types of infertility. Methods: Peripheral T lymphocyte subpopulations and cytokines in 33 consecutive cycles of IVF-ET were examined. All the women were stimulated with purified FSH and hCG after pituitary suppression with GnRH agonist. Peripheral blood samples were collected before FSH administration, on the day of hCG administration, the day of ET (day 2), day 6 and day 15. We measured plasma estradiol and progesterone levels and plasma interferon-,, interleukin-4 (IL-4), IL-10 and IL-12 levels. Peripheral T lymphocyte subpopulations, T helper type 1 and 2 cells (Th1 and Th2) and T cytotoxic type 1 and 2 cells (Tc1 and Tc2), were analyzed with three-color flowcytometry. Results: There were no changes in the plasma levels of the cytokines or in the proportions of Th1 and Th2 and the proportions of Tc1 and Tc2 in peripheral blood lymphocytes during the IVF-ET cycles. In women with endometriosis, the ratios of Tc1 to CD8+ lymphocytes and the Tc1 to Tc2 ratios before FSH administration were much higher than in women without endometriosis. The ratios of Tc1 to CD8+ lymphocytes were significantly lower in the patients with endometriosis who became pregnant. Conclusions: Peripheral cellular immunity does not change during IVF-ET cycles. In women with endometriosis, the peripheral Tc1 subpopulation is more predominant before ovarian stimulation, suggest- ing that the ratio of Tc1 before ovarian stimulation could be an indicator of fecundity for women with endometriosis. [source] Targeted immunotherapy of cancer: development of antibody-induced cellular immunityJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2003Yingjuan Lu ABSTRACT Although immunotherapy of cancer encompasses a large variety of distinct protocols, virtually all therapeutic strategies require the enabling/training of the immune system to distinguish tumour tissue from healthy tissue. In the case of antibody-based therapies, specificity obviously arises from the selectivity of the antibodies for tumour antigens, and tumour cell death derives from either direct cytotoxicity of the antibody or antibody-dependent cellular cytotoxicity. However, even when both of the above killing mechanisms are simultaneously active, we suggest that antibody-based immunotherapies may fall far short of their full potential. In this editorial, we first summarize the mechanisms by which current antibody-based therapies mediate cancer cell removal, and then propose two strategies by which this class of immunotherapies might be further improved. These suggested improvements involve the decoration of tumour cell surfaces with foreign haptens against which an endogenous humoral immune response can be mounted and the recruitment of the cellular arm of the immune system in an antibody-dependent process. [source] Specific Alteration of Peripheral Cytotoxic Cell Perforin Expression in Alcoholic Patients: A Possible Role in Alcohol-Related DiseasesALCOHOLISM, Issue 11 2003Pascal Perney Background: The association between chronic alcohol consumption and an increasing risk of infectious and neoplastic disease is related to an impairment of cellular immunity. However, studies of the number and activity of lymphocyte subsets show highly variable results. The aim of this study was to assess the expression of perforin, one of the main molecular agents of T and natural killer (NK) cell,mediated cytotoxicity, in alcoholic patients without cirrhosis. Methods: Eighteen patients with chronic alcoholism were prospectively included and compared with 18 age- and sex-matched healthy volunteers. Signs of hepatic insufficiency or portal hypertension, viral co-infection, other serious medical illness, and immune-related medications were exclusion criteria. Lymphocyte phenotype was assessed, and perforin expression was analyzed by flow cytometry in CD3+CD56+ T cells and NK cells. Granzyme synthesis was also evaluated in 11 of the 18 patients and compared with that of 11 age- and sex-matched controls. Results: The mean number of white blood cells and lymphocytes was not different between the controls and alcoholic patients, whereas the mean number of NK cells was significantly decreased in alcoholic patients (110 ± 79/mm3 versus 271 ± 192/mm3; p < 0.03). Perforin expression in T CD3+/CD56+ and in NK cells was significantly decreased in alcoholic patients compared with controls: 16 ± 3% vs. 36 ± 4% (p < 0.03) and 65 ± 15% vs. 78 ± 9% (p= 0.04), respectively. The percentage of cells expressing granzyme was similar in both groups. Conclusions: A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases. [source] Tumor necrosis factor-, and interferon-, directly impair epithelial barrier function in cultured mouse cholangiocytesLIVER INTERNATIONAL, Issue 1 2003Hanada Shinichiro Abstract:Background/Aims: In primary biliary cirrhosis (PBC), cytokines from CD4 + T lymphocytes were suggested to contribute to the intralobular bile duct damage together with cellular immunity by CD8 + T lymphocytes. Recently, we reported that immunolocalization of 7H6 , a tight junction (TJ)-associated protein , was significantly diminished in cholangiocytes in the PBC liver. In this study, we examined the direct effects of several cytokines , tumor necrosis factor-, (TNF-,), interferon-, (IFN-,), interleukin-2 and 4 (IL-2 and 4) , on TJ in immortalized mouse cholangiocytes. Moreover, we examined the inhibitory effect of ursodeoxycholic acid (UDCA)on cytokine-induced changes in paracellular permeability. Methods: Barrier function of TJ was evaluated by measuring transepithelial electrical resistance (TER) and 3H-inulin flux. We also performed immunostaining and immunoblotting for TJ-associated proteins , claudin-1 and -3, occludin, zonula occluden-1 (ZO-1) and 7H6. Results: TNF-, and IFN-,, but neither IL-2 nor IL-4, significantly decreased TER (P < 0.005). 3H-inulin flux studies confirmed IFN-,-induced increases in paracellular permeability of cholangiocytes (P < 0.001). In immunostaining and immunoblotting studies, TJ-associated proteins were well preserved in TNF-,- or IFN-,-treated cells. Ursodeoxycholic acidhas been found to have no inhibitory effect on increased paracellular permeability induced by TNF-, or IFN-,. Conclusion: These findings show that TNF-, and IFN-, disrupt barrier function of TJ in cholangiocytes without major structural changes to TJ and suggest that disruption of TJ function and subsequent leakage of the bile constituents may influence the aggravation of cholestasis in PBC. [source] Hepatitis B virus cellular immunity after liver transplantation: A role in preventing hepatitis B virus recurrence?,LIVER TRANSPLANTATION, Issue 3 2009Anne Marie Roque-Afonso [source] Role of CD4+ and CD8+ T-cells in the induction of oral tolerance to Actinomyces viscosus in miceMOLECULAR ORAL MICROBIOLOGY, Issue 3 2006W. Sosroseno Mucosal presentation of Actinomyces viscosus results in the induction of antigen specific systemic suppressor cells in mice. The aim of the present study was to determine the phenotype of the suppressor cells responsible for the induction of oral tolerance to low doses of A. viscosus. When CD8 cell-depleted DBA/2 mice were intragastrically immunized and systemically immunized with A. viscosus, the delayed type hypersensitivity response was suppressed but not the levels of antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4+ cells to CD4+ -depleted mice resulted in suppression of delayed type hypersensitivity response but not of the levels of antigen specific serum antibodies. In contrast, adoptive transfer of orally immunized CD8+ cells to CD8+ -depleted mice resulted in partially suppressed delayed type hypersensitivity response but significantly inhibited the levels of antigen specific serum antibodies. When orally tolerized CD8+ cells were cocultured with systemically immunized CD8+ cell-depleted spleen cells, splenic specific antibodies were inhibited. However, no suppression of splenic specific antibodies could be observed in the cultures containing orally tolerized CD4+ cells and systemically immunized CD4+ cell-depleted spleen cells. The results of the present study suggest that oral tolerance of humoral and cellular immunity induced by low doses of A. viscosus may be mediated by CD8+ and CD4+ cells, respectively. [source] | |||||||||||||||||||||||||||||||