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Persistent Infections (persistent + infections)
Selected AbstractsT-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3, conventional CD4 T cells and induction of CD4 T-cell anergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Lena Eroukhmanoff Abstract Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3× SEB) is partially due to an increased frequency of Foxp3+ CD4 T cells. Importantly, reduced number of conventional CD25, Foxp3, cells, rather than conversion of such cells to Foxp3+ cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3× OVA) and OVA,peptide (OVAp) (3× OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3× OVAp and 3× SEB mice. However, the in vivo anergy was CD4 T-cell autonomous and independent of Foxp3+ Treg. Finally, proliferation of transferred CD4 T cells was inhibited in repeatedly immunized mice but inhibition was lost when transfer was delayed, despite the maintenance of elevated frequency of Foxp3+ cells. These data provide important implications for Foxp3+ cell-mediated tolerance in situations of repeated antigen exposure such as human persistent infections. [source] Effects of HCV proteins in current HCV transgenic modelsHEPATOLOGY RESEARCH, Issue 2 2010Jian Jiao Hepatits C virus (HCV) is an enveloped virus with positive-sense single-stranded RNA genome that causes both acute and persistent infections associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma, which needs fully functional human hepatocytes for its development. Due to the strict human tropism of HCV, only human and higher primates such as chimpanzees have been receptive to HCV infection and development, cognition about pathophysiololgy and host immune responses of HCV infection is limited by lacking of simple laboratory models of infection for a long time. During the past decade, gene transfer approaches have been helpful to the understanding of the molecular basis of human disease. Transgenic cell lines, chimeric and transgenic animal models were developed and had been demonstrated their invaluable benefits. This review focuses on the existing HCV transgenic models and summarize the relative results about probable pathophysical changes induced by HCV proteins. [source] Clearance of hepatitis C in chimpanzees is associated with intrahepatic T-cell perforin expression during the late acute phaseJOURNAL OF VIRAL HEPATITIS, Issue 4 2010H. Watanabe Summary., The liver is the primary site of hepatitis C virus (HCV) replication. Therefore, we undertook detailed intrahepatic studies of T-cell dynamics, apoptosis, and gene expression during the acute phase of infection using liver biopsies from chimpanzees that developed persistent infection or spontaneously cleared the virus. We examined more than 40 liver biopsies histologically and quantitatively for T-cell infiltration, hepatocyte apoptosis and perforin expression. These data were correlated with outcome and viral kinetics. We observed intrahepatic T-cell infiltration in both groups of animals with CD8+ T cells representing the major population. The appearance of T cells was always associated with apoptosis and mild alanine aminotransferase (ALT) elevations. Apoptosis (5,20% of hepatocytes) always occurred prior to serum ALT peak. Quantification of intrahepatic ALT mRNA revealed no upregulation of gene expression confirming that serum ALT increases were due to release of this enzyme from cells. During the late acute phase, cleared animals showed an increased frequency of hepatocyte apoptosis relative to persistently infected animals (P < 0.05). This correlated with a higher intrahepatic CD8+ T-cell frequency in the cleared group (P < 0.01) with a greater proportion of lymphocytes expressing perforin compared with the persistent group (P < 0.001). All infected animals mounted intrahepatic immune responses during the acute phase, but these were not maintained in frequency or efficacy in persistent infections. There is a reduction in the numbers of intrahepatic T cells during the late acute phase in infections that become persistent with significantly fewer of these cells functional in clearing the virus by killing infected hepatocytes. [source] Current concepts on human papillomavirus infections in childrenAPMIS, Issue 6-7 2010STINA SYRJÄNEN Syrjänen S. Current concepts on human papillomavirus infections in children. APMIS 2010; 118: 494,509. Current evidence is strong enough to conclude that human papillomavirus (HPV) can be transmitted both sexually and non-sexually. The debate on HPV infections in children still continues but it is more focused on HPV prevalence than on transmission modes. HPV DNA detection in amniotic fluid, foetal membranes, cord blood and placental trophoblastic cells all suggest HPV infection in utero, i.e. prenatal transmission. Based on recent meta-analysis, vertical transmission occurs in approximately 20% of cases. Most of the mucosal HPV infections in infants are incident, persistent infections in oral and genital mucosa being found in less than 10% and 2% respectively. The mother seems to be the main transmitter of HPV to her newborn, but subsequent HPV infections are acquired horizontally via saliva or other contacts. Bimodal peak prevalence is seen for skin warts, oral papillomas and recurrent respiratory papillomatosis (RRP) in younger and older age groups, suggesting similar epidemiology. Of the clinical HPV diseases, juvenile-onset-RRP and genital condylomata are problematic; the former because of its life-threatening potential and the latter because of possible sexual abuse. HPV6 and 11 are the most common genotypes in both the lesions. Early in life, infections by the high-risk HPV genotypes may also remain persistent for a considerable period, and should be of considerable importance for HPV vaccination strategies. [source] Identification of candidate genes for schizophrenia based on natural resistance to infectious diseasesACTA NEUROPSYCHIATRICA, Issue 3 2003James S Brown Jr Background:, Identification of candidate genes for schizophrenia may be more successful than genome screens as the latter have not found consistent linkages. Objective:, To assist in the gene search, a model of schizophrenia based on resistance to infectious diseases, rather than susceptibility, is proposed. The theory blends the geography of schizophrenia with the assumption that genes that cause schizophrenia likely evolved and persist from selection pressure. The theory includes the notion that schizophrenia enhances biological survival at the cost of psychological and social functioning. Method:, To demonstrate the utility of using this model, the Medline literature was searched for resistance genes, mostly identified in mice. Results:, Based on homologous locations in the human genome, these resistance genes are shown to be located in human chromosome regions linked significantly, in at least one genome screen, with schizophrenia or some physiologically related function or condition associated with schizophrenia. Conclusions:, The infectious disease resistance theory of schizophrenia is offered as a viable model for understanding the origins of schizophrenia. The theory also allows for the inclusion of persistent infections, seasonal variability and translational pathophysiology to contribute to the etiology of schizophrenia. [source] Mycobacterium tuberculosis infection may protect against allergy in a tuberculosis endemic areaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2006C. C. Obihara Summary Background Epidemiological studies have shown an inverse relation of mycobacterial infection and the frequency of allergic diseases and asthma. Recent evidence suggests that allergic inflammation may be inhibited in the presence of chronic and persistent infections, such as that by Mycobacterium tuberculosis (MTB). The relation of tuberculin skin test (TST) size, an accepted marker of MTB infection and the frequency of allergic disease symptoms has not been reported from an area where MTB infection is endemic. Objective To investigate the association of TST and allergic disease symptoms, in children living in a tuberculosis (TB) endemic area. Methods In this cross-sectional study, 841 children aged 6,14 years from randomly selected household addresses in two poor communities of Cape Town, South Africa, were investigated with TST and standardized International Study on Asthma and Allergies in Childhood-based questionnaire on allergic disease symptoms. Results Children with positive TST (10 mm) were significantly less likely to have allergic disease symptoms, in particular allergic rhinitis (AR) (adjusted odds ratio 0.43; 95% confidence interval 0.24,0.79) than those with negative TST. This association remained significant after adjusting for possible confounders and correcting for the effect of clustering (>1 child per household address) in the sample. There was a significant inverse linear trend in the relation of TST size in millimetre and the frequency of allergic disease symptoms, in particular AR (P<0.001). Conclusions These results of inverse association of strong TST reaction and allergic disease symptoms in children from a TB endemic area are in support of the hypotheses that allergic inflammation may be inhibited by chronic infections, such as MTB. [source] | ||||||||||