Frontiers in Immunology · 2021 · 12 citations · 33 references
Life SciencesCell BiologyImmunologyAgingCellular ImmunologyInflammationAntiretroviral TherapyCell-mediated ImmunityImmunological MemoryLymphocyte ActivationT Cell ActivationT Cell BiologyAging-related Immune DysfunctionAging-related ImmunosuppressionCd8 Positive T Cell DifferentiationCd8 Positive T CellsHiv-associated ImmunosuppressionImmune System AgingSenescenceT-cell Immune Responses
Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8 + T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8 + T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8 + T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8 + T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8 + T-cell senescence and dysfunction in PLWH.
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