title: CD8 T-cell proliferative capacity is compromised in primary HIV-1 infection.
abstract: Understanding the correlates of immunity that control HIV-1 infection is imperative to our understanding of HIV-1 disease and vaccine development. HIV-1-specific cytotoxic T lymphocytes are fundamental to the control of viremia; however, which T-cell repertoire components enact this control remains unclear. We hypothesize that polyfunctional HIV-1-specific CD8 T cells capable of viral control are present in most patients early in infection and these cells are distinguished by their ability to secrete interleukin (IL)-2 and proliferate. We examined HIV-1-specific CD8 T-cell proliferation and cytokine secretion in primary HIV-1 infection (PHI) using known HIV-1 cytotoxic T-cell epitopes to exclude CD4 bystander effect. We found that only a subset of patients with PHI demonstrated "CD4-independent" CD8 proliferation ex vivo. The remainder of the patients lacked HIV-1-specific CD8 T cells with proliferative capacity, even after the addition of exogenous IL-2. Among the proliferators, IL-2 production from the total HIV-specific CD8 T-cell population correlated with proliferation. Surprisingly, though, we did not routinely detect both IL-2 secretion and proliferative capacity from the same antigen-specific CD8 T cells. Thus, there are distinct and heterogeneous populations of CD8 T cells, phenotypically characterized by either proliferation or IL-2 secretion and few with dual capacity. Generation of these responses may be an important measure of HIV-1 control but are not universal after PHI. Furthermore, the heterogeneity of this population suggests that a simple measure of an effective vaccine response remains elusive.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. heaths@uab.edu
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heath
authors.forename: Steffanie
authors.initials: S
authors.lastname: Sabbaj
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: J Michael
authors.initials: JM
authors.lastname: Kilby
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology
chemical_list: D007376:Interleukin-2