Background: The REACH Project (Reaching for Excellence in Adolescent Care and Health) of the Adolescent Medicine HIV/AIDS Research Network is an observational study of HIV-infected- and high-risk HIV-uninfected adolescents, ages 13–18 yrs at enrollment from 15 different clinical sites in 13 U.S. cities. These youth acquire HIV infection through risk behaviors, primarily sexual activity. Understanding the immunological effects of HIV infection in this population is important in order to develop appropriate therapeutic strategies. Earlier, we have shown that HIV-infected adolescents manifest increased proportions of CD8 T-cells with naive phenotypic markers as compared to uninfected high risk, age-matched subjects. In this study our aim was to determine whether HIV infection disrupts TCR Vb repertoire and leads to abnormal thymus function in treatment naïve adolescents.

Methods: The studies were performed in subpopulations of treatment naïve, HIV-infected adolescents and high-risk HIV-negative adolescents in purified CD4 and CD8 T-cells isolated from cryopreserved cell samples. TCR Vb repertoire was determined by CDR3 length spectra-typing and thymus function was investigated by T-cell receptor excision circles (TRECs). The relationships of these immunologic characteristics with each other, and with plasma HIV viral load and T-cell surface markers were determined.

Results: HIV-infected adolescents (n = 11) exhibited significantly greater perturbations in their TCR Vb repertoire in comparison to HIV-negative subjects (n = 7). Perturbations in the CD8 T-cell compartment were more profound in comparison to CD4 T-cells. The CD4 TCR Vb perturbations were negatively correlated with the total and phenotypic naïve CD4 T-cells, and with CD4 TRECs. CD8 TRECs, although not correlated with CD8 TCR Vb 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 (n = 34) and uninfected adolescents (n = 17).

Conclusions: The TCR Vb repertoire in adolescents is profoundly perturbed even in early stages of HIV infection, when CD4 counts in most subjects are within normal limits. The correlative analyses demonstrating negative association of CD4 TRECs with CD4 TCR Vb perturbations and of CD8 TRECs with CD8 activation markers provide evidence for the intense activation of the central and peripheral immune compartments in this study population.