CD4 + and CD8 + T Cell Receptor Repertoire Perturbations with Normal Levels of T Cell Receptor Excision Circles in HIV-Infected,Therapy-Naive Adolescents

Abstract

Our objective was to determine whether treatment-naive HIV-infected adolescents manifest abnormalities in thymus function and peripheral T cell repertoire, and to assess relationships of these immunologic characteristics with each other, with plasma HIV virus load, and T cell surface markers. TCR Vβ repertoire was determined by CDR3 length spectratyping in purified CD4⁺ and CD8⁺ T cells of high-risk, HIV-negative adolescents and of treatment-naive, HIV-infected adolescents. Thymus function was investigated by the simultaneous examination of T cell receptor excision circles (TRECs) in the CD4⁺ and CD8⁺ T cell subsets. HIV-infected adolescents exhibited significantly greater perturbations in their TCR Vβ repertoire in comparison with HIV-negative subjects. Perturbations in the CD8⁺ T cell compartment were more profound in comparison with CD4⁺ T cells. The CD4⁺ TCR Vβ perturbations were negatively correlated with the total and phenotypically naive CD4⁺ T cells, and with CD4⁺ TRECs. CD8⁺ TRECs, although not correlated with CD8⁺ TCR Vβ perturbations, showed negative correlation with memory and activated CD8⁺ T cells. Interestingly, TRECs in CD4⁺ and CD8⁺ T cells were not significantly different between HIV-infected and uninfected adolescents. The TCR Vβ repertoire in adolescents is profoundly perturbed even in early stages of HIV infection, when total CD4⁺ cell counts in most subjects are within normal limits. The correlative analyses demonstrating negative association of CD4⁺ cell TRECs with CD4⁺ TCR Vβ perturbations and of CD8⁺ TRECs with CD8⁺ cell activation markers provide evidence of the intense activation of the central and peripheral immune compartments in this study population.