Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8+ T cells in HIV/TB co-infection

• HIV/TB co-infection increases plasma HIV viremia and decreases CD4/CD8 T-cell ratio.
• Close association between the expression of CD38 and CD57 on late-senescent CD8+ T cells.
• T cells of HIV-infected and HIV/TB co-infected individuals reveal comparable accentuation in HLA-DR levels.
• CD8+ T-cell subsets of HIV/TB co-infected patients show significantly increased levels of CD57 and altered expression of phenotypic markers.
• Diminished intracellular secretion of IFN-γ, perforin and granzyme B, and increased levels of intracellular CD57 in HIV-specific CD8+ T cells of HIV/TB co-infected patients.

The role of T-cell immunosenescence and functional CD8+ T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8+ T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8+ T cells, besides diminished expression of CD127 (IL-7Rα) on CD57+CD4+ T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8+ T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8+ T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8+ T cells.