Premature Aging of T cells Is Associated With Faster HIV-1 Disease Progression

Abstract

Objective: To determine if untreated HIV-1 infection and progression is associated with premature aging of memory CD8⁺ and CD4⁺ T cells and naive CD4⁺ T cells. Methods: Twenty HIV-1-infected fast progressors and 40 slow progressors were included in our study, using risk set sampling. The expression of cell surface markers reflecting the differentiation stages of lymphocytes was measured using flow cytometry analyses performed on cryopreserved peripheral blood mononuclear cells. Results: We found that HIV-1 disease progression is associated with a decreased CD28 median florescence intensity on CD4⁺ and CD8⁺ T cells; an increased proportion of intermediate- and late-differentiated CD8⁺ T cells and a decreased CD31 median florescence intensity on naive CD4⁺ T cells of recent thymic origin. A selective depletion of peripherally expanded naive CD4⁺ T cells was found to be associated with HIV-1 infection but not with HIV-1 disease progression. Conclusions: The overall change during HIV-1 infection and progression is associated with a shift in the T-cell population toward an aged conformation, which may be further compromised by impaired renewal of the less-differentiated CD4⁺ T-cell population. Our results suggest that HIV-1 infection induces an accelerated aging of T lymphocytes, which is associated with the clinical progression to AIDS and death.