Suppression of HIV-specific T cell activity by lymph node CD25⁺ regulatory T cells from HIV-infected individuals

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 104; no. 9; pp. 3390 - 3395
• Main Authors: Kinter, Audrey, McNally, Jonathan, Riggin, Lindsey, Jackson, Robert, Roby, Gregg, Fauci, Anthony S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.02.2007; National Acad Sciences
• Subjects: AIDS; Biological Sciences; Blood; CD4-positive T-lymphocytes; Cell Proliferation; Cells; Cultured cells; Cytokines; disease course; Disease Progression; HIV; HIV infections; HIV Infections - immunology; Human immunodeficiency virus; Humans; immune response; Lymph nodes; Lymph Nodes - cytology; Lymphatic system; Lymphocyte receptors; Lymphoid tissue; patients; T cell receptors; T lymphocytes; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - virology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - virology; T-Lymphocytes, Regulatory - immunology; Viral load; Viremia
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0611423104

CD25⁺ CD4⁺ FoxP3⁺ regulatory T (Treg) cells isolated from the peripheral blood of asymptomatic HIV-infected individuals have been demonstrated to significantly suppress HIV-specific immune responses in vitro. CD25⁺ Treg cell suppressor activity in the peripheral blood seems to diminish with progression of HIV disease, and it has been suggested that loss of Treg cells contributes to aberrant immune activation and disease progression. However, phenotypic studies suggest that Treg cells may migrate to, and be maintained or even expanded in, tissue sites of HIV replication. Currently, it is not known whether tissue-associated Treg cells maintain suppressive activity in the context of HIV infection, particularly in individuals with advanced disease. The present study demonstrates that CD25⁺ Treg cells isolated from lymph nodes and peripheral blood of HIV⁺ subjects, even those with high viral loads and/or low CD4⁺ T cell counts, maintain potent suppressive activity against HIV-specific cytolytic T cell function. This activity was better in lymph node as compared with peripheral blood, particularly in patients with high levels of plasma viremia. In addition, the expression of certain CD25⁺ Treg-associated markers on CD4⁺ T cells isolated from lymph nodes differed significantly from those on CD4⁺ T cell subsets isolated from the peripheral blood. These data suggest that CD25⁺ Treg cell-mediated suppression of HIV-specific responses continues throughout the course of HIV disease and, because of their particularly potent suppression of HIV-specific CTL activity in lymphoid tissue, may considerably impact the ability to control HIV replication in vivo.