title: 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.affiliation: University of Alabama at Birmingham, Department of Medicine, Birmingham, AL 35294, USA.
authors.forename: LaTonya D
authors.initials: LD
authors.lastname: Williams
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Steffanie
authors.initials: S
authors.lastname: Sabbaj
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Zajac
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D015331:Cohort Studies; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; D000098546:Interleukin-21