Lack of CD28 expression on HIV‐specific cytotoxic T lymphocytes is associated with disease progression

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Abstract
During HIV infection, CD8+ T cells lacking the costimulatory molecule CD28 increase in number and proportion. This accumulation is associated with disease activity and possibly with CD8+ T-cell dysfunction. In this study, CD8+CD28+ and CD8+CD28− T cells from 41 HIV-infected individuals at various stages of disease were compared in terms of HIV-specific cytotoxicity, TCRβV repertoire diversity, and cytokine production. We found that the CD28 phenotype of anti-HIV CTL evolves in parallel with disease progression and disease activity. Absolute numbers of CD4+ T cells and CD4+/CD8+ T-cell ratios progressively decreased in 3 groups with an increasing prevalence of CD28− HIV-specific CTL. Conversely, HIV replication levels progressively increased in parallel with the prevalence of CD28− HIV-specific CTL. Repertoire diversity at the level of TCRβV gene family expression was maintained at normal levels for both CD28+ and CD28− T cells at all stages of infection. Diversity at the level of junctional length polymorphism was more restricted in the CD8+CD28− T-cell population, but this difference remained relatively constant through different stages of infection. Both CD28+ and CD28− T cells produced IL-2 and IFN-γ, regardless of disease stage and/or the predominant CD28 phenotype of anti-HIV CTL.
Funding Information
  • Canadian Institutes of Health Research (HOP37490)
  • Canadian Foundation for AIDS Research (CANFAR)/CIHR PhD fellowship

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