Regulatory T cells

IL-12 induces CD4+CD25− T cell activation in the presence of T regulatory cells. King, I. L. & Segal, B. M. J. Immunol. 175, 641–645 (2005)

This study provides another explanation for the pro-inflammatory, T-helper-1-cell-inducing effects on CD4+ T cells of interleukin-12 (IL-12) produced by myeloid cells. CD4+ T cells can escape suppression mediated by CD4+CD25+ regulatory T (TReg) cells in in vitro co-cultures through IL-12-mediated support of activation, proliferation and cytokine production. This effect was not reproduced by the related family member IL-23 or by indirect effects on interferon-γ production, and it required expression of the IL-12 receptor by the effector T cells but not by the TReg cells. The authors suggest that, in an inflamed microenvironment, IL-12 blocks immunoregulation by TReg cells to allow an effective immune response.

Asthma and allergy

Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. Rangasamy, T. et al. J. Exp. Med. 202, 47–59 (2005)

Oxidative stress as a result of inflammation is thought to be involved in asthma pathogenesis, but until now, there has been little direct evidence that a defect in anti-oxidant pathways might contribute to disease. This paper shows that mice with disruption of the Nrf2 gene — which encodes a redox-sensitive transcriptional regulator of anti-oxidant genes — have increased allergen-driven airway inflammation associated with increased levels of oxidative-stress markers. Future studies looking for an association between variation in the NRF2 response and asthma susceptibility in humans will help to determine the general importance of maintaining an oxidant–anti-oxidant balance in the lungs.

HIV

Macrophages archive HIV-1 virions for dissemination in trans. Sharova, N. et al. EMBO J. 24, 2481–2489 (2005)

Most research has focused on understanding the mechanisms of HIV-1 persistence in CD4+ T cells; however, macrophages can also function as cellular reservoirs of the virus. Sharova et al. found that, after a single cycle of HIV-1 infection, macrophages could sustain de novo production of virions that were able to infect lymphocytes in trans. If macrophage production of virus was blocked using a protease inhibitor, the level of infectious virus produced by the macrophages decreased rapidly for the first week after treatment. However, after this time, the decrease in the level of infectious virus was much slower, and infectious virions could be detected 5 weeks after exposure to the protease inhibitors. This study indicates that some virions are relatively stable in macrophages, leading the authors to suggest that macrophages contribute to HIV-1 persistence in the host.