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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques.

Regulatory T (T(reg)) cells are a subset of CD25(+)CD4(+) T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T-cell activation and effector functions. T(reg) cells are increased in tissues of individuals infected with HIV-1 and macaques infected with simian immunodeficiency virus (SIV(mac251)). In HIV-1 infection, T(reg) cells could exert contrasting effects: they may limit viral replication by decreasing immune activation, or they may increase viral replication by suppressing virusspecific immune response. Thus, the outcome of blocking T(reg) function in HIV/ SIV should be empirically tested. Here, we demonstrate that CD25(+) T cells inhibit virus-specific T-cell responses in cultured T cells from blood and lymph nodes of SIV-infected macaques. We investigated the impact of CTLA-4 blockade using the anti-CTLA-4 human antibody MDX-010 in SIV-infected macaques treated with antiretroviral therapy (ART). CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme IDO and the level of the suppressive cytokine transforming growth factor-beta (TGF-beta) in tissues. CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4(+) and CD8(+) T cells. Therefore, blunting T(reg) function in macaques infected with SIV did not have detrimental virologic effects and may provide a valuable approach to complement ART and therapeutic vaccination in the treatment of HIV-1 infection.[1]


  1. CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques. Hryniewicz, A., Boasso, A., Edghill-Smith, Y., Vaccari, M., Fuchs, D., Venzon, D., Nacsa, J., Betts, M.R., Tsai, W.P., Heraud, J.M., Beer, B., Blanset, D., Chougnet, C., Lowy, I., Shearer, G.M., Franchini, G. Blood (2006) [Pubmed]
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