HIV-1-Specific Interleukin-21 + CD4 + T Cell Responses Contribute to Durable Viral Control through the Modulation of HIV-Specific CD8 + T Cell Function
- 15 January 2011
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 85 (2), 733-741
- https://doi.org/10.1128/jvi.02030-10
Abstract
Functional defects in cytotoxic CD8 + T cell responses arise in chronic human viral infections, but the mechanisms involved are not well understood. In mice, CD4 cell-mediated interleukin-21 (IL-21) production is necessary for the maintenance of CD8 + T cell function and control of persistent viral infections. To investigate the potential role of IL-21 in a chronic human viral infection, we studied the rare subset of HIV-1 controllers, who are able to spontaneously control HIV-1 replication without treatment. HIV-specific triggering of IL-21 by CD4 + T cells was significantly enriched in these persons ( P = 0.0007), while isolated loss of IL-21-secreting CD4 + T cells was characteristic for subjects with persistent viremia and progressive disease. IL-21 responses were mediated by recognition of discrete epitopes largely in the Gag protein, and expansion of IL-21 + CD4 + T cells in acute infection resulted in lower viral set points ( P = 0.002). Moreover, IL-21 production by CD4 + T cells of HIV controllers enhanced perforin production by HIV-1-specific CD8 + T cells from chronic progressors even in late stages of disease, and HIV-1-specific effector CD8 + T cells showed an enhanced ability to efficiently inhibit viral replication in vitro after IL-21 binding. These data suggest that HIV-1-specific IL-21 + CD4 + T cell responses might contribute to the control of viral replication in humans and are likely to be of great importance for vaccine design.This publication has 24 references indexed in Scilit:
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