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Naive and Memory CD4(+) T Cells Are Differentially Affected in Indonesian HIV Patients Responding to ART.

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Tanaskovic S, Fernandez S, Saraswati H, Yunihastuti E, Gani RA, Djauzi S, Price P,


Tanaskovic S, Fernandez S, Saraswati H, Yunihastuti E, Gani RA, Djauzi S, Price P, (click to view)

Tanaskovic S, Fernandez S, Saraswati H, Yunihastuti E, Gani RA, Djauzi S, Price P,

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Viral immunology 29(3) 176-83 doi 10.1089/vim.2015.0108

Abstract

While most HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency recover CD4(+) T cell numbers, the profiles and functions of the newly acquired CD4(+) T cells have not been monitored in a resource-limiting setting. In this study, HIV patients (n = 31) from Jakarta, Indonesia, were studied 9 months after commencing ART with nadir CD4(+) T cell counts <200 cells/μL. All patients were hepatitis C virus (HCV) seropositive, but asymptomatic. Twelve healthy age-matched controls from the same community were included. CD4(+) T cell subsets, immune activation (HLA-DR), and expression of the interleukin (IL)-7 receptor α chain (CD127) were quantitated by flow cytometry. Proliferation (expression of Ki67) was measured following in vitro stimulation (5 days) with anti-CD3 antibody or IL-7. Fifty-two percent of patients recovered CD4(+) T cell counts >200 cells/μL over 12 months. At 9 months, patients had fewer naive and CD31(+)-naive CD4(+) T cells, more effector memory (EM) CD4(+) T cells, and higher HLA-DR expression on CD4(+) T cells than controls. CD127 expression was low on all CD4(+) T cell subsets except for naive cells, where it was similar to controls. Similarly, after anti-CD3 antibody or IL-7 stimulation, patients had lower Ki67 expression than controls in all subsets, except naive CD4(+) T cells where it was normal or elevated. Overall in the first year of ART, patients had fewer naive and more EM CD4(+) T cells. Ongoing immune activation and, antigen-driven stimulation and differentiation of naive T cells may reduce the naive T cell pool, while driving the maturation and accumulation of memory cells with proliferative defects.

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