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The "privileged" liver and hepatic tolerogenicity.

The mechanism underlying the immunological advantage of hepatic allografts relative to other organs is incompletely understood. We used molecular probes for the repetitive units on the Y chromosome, to identify an increasing number of male liver venous endothelial cells in needle biopsy samples of men who received female donor liver grafts. We have also shown repopulation of liver endothelium by bone marrow derived cells in a male to female mouse bone marrow transplant model. We conclude that the liver has unique venous endothelium characterized by turnover and replacement by bone marrow derived cells

Prospects for Universal Influenza Virus Vaccine

The current vaccination strategy against influenza A and B viruses is vulnerable to the unanticipated emergence of epidemic strains that are poorly matched by the vaccine. A vaccine that is less sensitive to the antigenic evolution of the virus would be a major improvement. The general feasibility of this goal is supported by studies in animal models that show that immunologic activities directed against relatively invariant viral determinants can reduce illness and death. The most promising approaches are based on antibodies specific for the relatively conserved ectodomain of matrix protein 2 and the intersubunit region of hemagglutinin. However, additional conserved determinants for protective antibodies are likely to exist, and their identification should be encouraged. Most importantly, infection and current vaccines do not appear to effectively induce these antibodies in humans. This finding provides a powerful rationale for testing the protective activity of these relatively conserved viral components in humans

A Regulatory Role for TRAF1 in Antigen-induced Apoptosis of T Cells

Tumor necrosis factor receptor (TNFR)–associated factor 2 (TRAF2) and TRAF1 were found as components of the TNFR2 signaling complex, which exerts multiple biological effects on cells such as cell proliferation, cytokine production, and cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-κB, but the role of TRAF1 has not been previously determined. Here we show in transgenic mice that TRAF1 overexpression inhibits antigen-induced apoptosis of CD8+ T lymphocytes. Our results demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and also support the hypothesis that the combination of TRAF proteins in a given cell type determines distinct biological effects triggered by members of the TNF receptor superfamily

CD4+/CD8+ T lymphocytes imbalance in children with severe 2009 pandemic influenza A (H1N1) pneumonia

PurposeThis study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1) pneumonia, and to compare their clinical and immunological findings with those of control subjects.MethodsThirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group), 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group) and 13 control subjects (control group) were measured.ResultsTotal lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02). The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group (411.5±253.5/µL) than in the moderate pneumonia (644.9±291.1/µL, P=0.04) and control (902.5±461.2/µL, P=0.01) groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group (684.2±420.8/µL) than in the moderate pneumonia (319.7±176.6/µL, P=0.02) and control (407.2±309.3/µL, P=0.03) groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group (0.86±0.24) than in the moderate pneumonia (1.57±0.41, P=0.01) and control (1.61±0.49, P=0.01) groups. The serum levels of IgG, IgM and IgE were significantly higher in the severe pneumonia group than in the 2 other groups.ConclusionThe results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children

CD59a deficiency exacerbates influenza-induced lung inflammation through complement-dependent and-independent mechanisms

Influenza-specific immune activity not only promotes virus clearance but also causes immunopathology, thereby underlining the importance of mounting a measured anti-viral immune response. Since complement bridges both the innate and adaptive immune systems and has been implicated in defence against influenza, the role of the complement regulator CD59a in modulating the response to influenza was explored. For this purpose, immune responses to influenza virus, strain E61-13-H17, in mice deficient in the complement regulator protein CD59a (Cd59a–/– mice) were compared to those in wild-type mice. The severity of lung inflammation was significantly enhanced in the lungs of Cd59a–/– mice with increased numbers of infiltrating neutrophils and CD4+ T cells. When complement was inhibited using soluble complement receptor1, the frequency of lung-infiltrating neutrophils in influenza-infected Cd59a–/– mice was much reduced whilst numbers of CD4+ T cells remained unchanged. These results demonstrate that CD59a, previously defined as a complement regulator, modulates both the innate and adaptive immune response to influenza virus by both complement-dependent and-independent mechanisms