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.

• Authors: LaTonya D Williams, Anju Bansal, Steffanie Sabbaj, Sonya L Heath, Wei Song, Jianming Tang, Allan J Zajac, Paul A Goepfert
• Journal: Journal of virology (J Virol) Vol. 85 Issue 5 Pg. 2316-24 (Mar 2011) ISSN: 1098-5514 [Electronic] United States
• PMID: 21159862 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukins
• interleukin-21

Topics

• CD4-Positive T-Lymphocytes (immunology, virology)
• CD8-Positive T-Lymphocytes (immunology, virology)
• Cells, Cultured
• Cohort Studies
• HIV Infections (immunology, virology)
• HIV-1 (immunology, physiology)
• Humans
• Interleukins (immunology)