Functional CD8+ T Cell Responses and Immunosenescence in HIV-Tuberculosis Co-Infection

Esaki M Shankar1, Yee K Chong1, Alireza Saeidi1, Adeeba Kamarulzaman2, Marie Larsson3
Affiliates: 1Department of Medical Microbiology, University of Malaya, Faculty of Medicine, Kuala Lumpur, Malaysia 2Center for Excellence and Research in AIDS, University of Malaya, Faculty of Medicine, Kuala Lumpur, Malaysia 3Department of Clinical and Experimental Medicine, Linkoping University, 58185 Linkoping, Sweden

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The association between T-cell immunosenescence, HIV disease progression, and functional T-cell responses in HIV-TB co-infection is less well understood. Here, we correlated the surrogate markers of HIV disease progression with immune activation, immunosenescence, and markers of functional T cells of HIV-TB co-infected, mono-infected and healthy controls. We found that increased plasma viremia and reduced CD4:CD8 T-cell ratio in HIV-TB co-infected subjects correlated with increased expression of CD57 and markers consistent to late-senescent CD8+ T cells. Elevated levels of CD57 and CD38 were directly related to decreased expression of CD27 and CD28 on CD8+ T cells, besides diminished CD127, CD27 and CD28 levels on CD57+CD4+ T cells. Increased HIV viremia, decreased T-cell counts and CD4:CD8 T-cell ratio were linked to accentuated CD38 levels. Elevation of CD38, CD57 and decrease of CD27, CD127 and CD28 on CD8+ T cells were associated with surrogate markers of disease progression. T-cell activation with MTB antigen, HIV gag p24 and PHA in HIV-TB co-infected subjects led to diminished synthesis of intracellular perforin, granzyme B and IFN-γ by antigen-specific CD8+ T cells. Together, HIV-TB co-infection elevated immunosenescence, chronic immune activation, and functionally deficient CD8+ T cells, which potentially contribute to accelerated HIV disease progression.