Frontline : Polyfunctional T cell responses are a hallmark of HIV-2 infection

HIV‐2 is distinguished clinically and immunologically from HIV‐1 infection by delayed disease progression and maintenance of HIV‐specific CD4+ T cell help in most infected subjects. Thus, HIV‐2 provides a unique natural human model in which to investigate correlates of immune protection against HIV disease progression. Here, we report a detailed assessment of the HIV‐2‐specific CD4+ and CD8+ T cell response compared to HIV‐1, using polychromatic flow cytometry to assess the quality of the HIV‐specific T cell response by measuring IFN‐γ, IL‐2, TNF‐α, MIP‐1β, and CD107a mobilization (degranulation) simultaneously following Gag peptide stimulation. We find that HIV‐2‐specific CD4+ and CD8+ T cells are more polyfunctional that those specific for HIV‐1 and that polyfunctional HIV‐2‐specific T cells produce more IFN‐γ and TNF‐α on a per‐cell basis than monofunctional T cells. Polyfunctional HIV‐2‐specific CD4+ T cells were generally more differentiated and expressed CD57, while there was no association between function and phenotype in the CD8+ T cell fraction. Polyfunctional HIV‐specific T cell responses are a hallmark of non‐progressive HIV‐2 infection and may be related to good clinical outcome in this setting.