CD4+ and CD8+ T cell receptor repertoire perturbations with normal levels of T cell receptor excision circles in HIV-infected, therapy-naive adolescents

Savita Pahwa, Vivek Chitnis, Richard M. Mitchell, Sanjit Fernandez, Alamelu Chandrasekharan, Craig M. Wilson, Steven D. Douglas

Research output: Contribution to journalArticle

18 Scopus citations

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. Enterestingly, 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.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalAIDS research and human retroviruses
Volume19
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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