Innate immunity

Dual role of α-defensin-1 in anti-HIV-1 innate immunity. Chang, T. L. et al. J. Clin. Invest. 115, 765–773 (2005).

α-Defensin-1 — an antimicrobial peptide that is produced by neutrophils — has been shown to inhibit HIV-1 replication. In this study, Chang et al. found that α-defensin-1 directly inactivates HIV-1 virions but that this inactivation is abrogated in the presence of serum or increased numbers of virus particles. Instead, in the presence of serum, α-defensin-1 mediates its antiviral effects on the target cells. Interestingly, protein kinase C (PKC) phosphorylation was reduced in CD4+ T cells treated with α-defensin-1, and HIV-1 replication was blocked at similar stages in CD4+ T cells treated with either α-defensin-1 or an inhibitor of PKC-α and PKC-β. α-Defensin-1, therefore, mediates its cellular effects, at least in part, through inhibition of PKC-signalling pathways.

Viral immunity

Inverse correlation between IL-7 receptor expression and CD8 T cell exhaustion during persistent antigen stimulation. Lang, K. S. et al. Eur. J. Immunol. 35, 738–745 (2005).

Infection with lymphocytic choriomeningitis virus is characterized by persistence of the virus and is often associated with exhaustion of CD8+ T cells. In this study, the authors show that persistent viral antigen suppressed the expression of the interleukin-7 receptor α-chain (IL-7Rα) by antigen-specific T cells. Because IL-7 is associated with the survival of memory T cells, prolonged downregulation of its receptor correlated with diminished T-cell responses in chronically infected mice. By contrast, the presence of short-lived antigen resulted in only transient suppression of IL-7Rα expression and did not cause T-cell exhaustion, indicating that antigen longevity can determine T-cell fate.

T-cell responses

The role of herpesvirus entry mediator as a negative regulator of T cell-mediated responses. Wang, Y. et al. J. Clin. Invest. 115, 711–717 (2005).

Herpesvirus entry mediator (HVEM) has previously been described as a T-cell co-stimulatory receptor, but to the surprise of these researchers, HVEM-deficient T cells, when compared with wild-type T cells, showed increased proliferative responses after stimulation with CD3-specific antibody or exposure to concanavalin A (conA) in vitro. Furthermore, they showed that administration of conA to HVEM-deficient mice resulted in increased morbidity and mortality, owing to the development of severe T-cell-mediated hepatitis. And compared with wild-type splenocytes, conA-treated HVEM-deficient splenocytes produced higher levels of several cytokines. Finally, HVEM-deficient mice showed increased susceptibility to experimental allergic encephalomyelitis. Together, these results indicate that HVEM can function as a negative regulator of T-cell responses.