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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
CTLA-4 blockade decreases TGF-β, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques
Blood, Volume 108, No. 12, Year 2006
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Description
Regulatory T (Treg) 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. Treg cells are increased in tissues of individuals infected with HIV-1 and macaques infected with simian immunodeficiency virus (SIVmac251). 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 virus-specific immune response. Thus, the outcome of blocking Treg 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-β (TGF-β) 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 Treg 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. © 2006 by The American Society of Hematology.
Authors & Co-Authors
Hryniewicz, Anna
Unknown Affiliation
Boasso, Adriano
Unknown Affiliation
Vaccari, Monica
Unknown Affiliation
Fuchs, Dietmar N.
Unknown Affiliation
Venzon, David J.
Unknown Affiliation
Betts, Michael R.
Unknown Affiliation
Tsai, Wenpo
Unknown Affiliation
Héraud, Jean Michel
Unknown Affiliation
Beer, Brigitte E.
Unknown Affiliation
Chougnet, Claire A.
Unknown Affiliation
Shearer, Gene M.
Unknown Affiliation
Franchini, Genoveffa
United States, Bethesda
National Institutes of Health Nih
Statistics
Citations: 143
Authors: 12
Affiliations: 1
Identifiers
Doi:
10.1182/blood-2006-04-010637
ISSN:
00064971
Research Areas
Infectious Diseases