Immune deficiencies, infection, and systemic immune disordersAntiretroviral therapy corrects HIV-1-induced expansion of CD8+CD45RA+CD27−CD11abright activated T cells

BackgroundHIV infection decreases thymic output and induces chronic T-cell activation.ObjectiveTo examine the reconstitution of naive and activated T cells.MethodsExtended immune phenotyping of CD4+ and CD8+ T-cell subsets was combined with T-cell receptor rearrangement excision circle (TREC) levels and measures of T-cell receptor repertoire perturbations in CD8+ T-cell subpopulation to define the global effect of HIV-1 on T-cell dynamics. Evaluations before and after therapy were performed in HIV-infected children and compared with those in healthy individuals.ResultsTen HIV-infected children and adolescents with a broad range of pretherapy CD4+ T-cell counts were compared with healthy individuals. Pretherapy late activated CD8+ T cells (CD3+CD8+CD45RA+CD27−CD11abright cells) were expanded among HIV-infected subjects. Successful antiretroviral therapy increased the proportion of naive T cells (CD3+CD4+CD45RA+CD27+CD28+ and CD3+CD8+CD45RA+CD27+CD11adim cells), with a significant decrease in late activated CD8+ T cells. The proportion of naive CD4+ and CD8+ T cells significantly predicted log10 TREC copies/106 PBMCs in infected children and healthy control subjects, with a negative correlation in late activated CD8+ T cells and activated CD4+ T cells. Treatment re-established Gaussian distributions and decreased oligoclonal expansion within the Vβ repertoire of CD8+CD45RA+ T cells, but compared with that seen in healthy children, the proportion of late activated CD8+ T cells remained increased.ConclusionHIV infection strikingly shifts the proportion of naive and late activated CD45RA+CD8+ T cells. Homeostasis within this T-cell population reflects TREC levels and the extent of T-cell receptor Vβ perturbations.