Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers.

Abstract

A hallmark of human immunodeficiency virus type 1 (HIV-1) pathogenesis is the rapid loss of CD4 T cells leading to generalized immune dysfunction, including an exhausted CD8 T cell phenotype. Understanding the necessary factors that govern the functional quality and protective potential of antiviral T cell responses would facilitate rational vaccine design and improve therapeutic strategies to combat persistent infections. Mouse models of chronic viral infection demonstrate that interleukin-21 (IL-21), produced primarily by CD4 T cells, is required for the generation and maintenance of functionally competent CD8 T cells and viral containment. We reasoned that preserved IL-21 production during HIV-1 infection would be associated with enhanced CD8 T cell function, allowing improved viral control. Here we analyzed the ability of CD4 and CD8 T cells to produce several cytokines in addition to IL-21 ex vivo following stimulation with overlapping HIV-1 peptides. Both CD4 and CD8 T cells were able to produce IL-21 in response to HIV-1 infection, with the latter cell type more closely associated with viral control. Furthermore, IL-21-producing HIV-1-specific CD4 T cells (compared to those producing other cytokines) were the best indicator of functional CD8 T cells. Our results demonstrate that HIV-1-specific IL-21-producing CD8 T cells are induced following primary infection and enriched in elite controllers, suggesting a critical role for these cells in the maintenance of viremia control.

DOI: 10.1128/JVI.01476-10
01002002011201220132014201520162017
Citations per Year

509 Citations

Semantic Scholar estimates that this publication has 509 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Williams2011Interleukin21producingHC, title={Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers.}, author={LaTonya D Williams and Anju Bansal and Steffanie Sabbaj and Sonya L Heath and Wei Song and Jianming Tang and Allan J. Zajac and Paul A Goepfert}, journal={Journal of virology}, year={2011}, volume={85 5}, pages={2316-24} }