Combination antiretroviral therapy results in a rapid increase in T cell receptor variable region beta repertoire diversity within CD45RA CD8 T cells in human immunodeficiency virus-infected children

J Infect Dis. 2003 Feb 1;187(3):385-97. doi: 10.1086/367674. Epub 2003 Jan 24.

Abstract

Human immunodeficiency virus (HIV) type 1 disrupts the T cell receptor (TCR) variable region (V) beta repertoire in CD8 T cells by impairing thymic capacity and skewing postthymic cellular maturation. The TCR repertoire was examined using spectratyping of CDR3 length diversity within CD45RA and CD45RO CD8 T cells in HIV-infected and healthy children. In healthy children, CDR3 lengths displayed Gaussian distribution in both CD45RA and CD45RO subsets. Vbeta families in HIV-infected children displayed a large proportion of perturbations in both subsets. High virus load and advanced immunosuppression correlated with increased perturbations within CD45RA but not CD45RO CD8 T cells. After therapy and virus suppression, there was rapid reestablishment of Gaussian distributions in CD45RA cells. HIV-1-induced disruption of TCR diversity within CD45RA CD8 T cells correlates with disease progression. Suppression of viral replication by treatment results in the rapid correction of TCR diversity in this CD8 subset because of emergence of new T cells from the thymus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Child
  • Female
  • Gene Expression Regulation
  • HIV
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Infant
  • Leukocyte Common Antigens / analysis
  • Leukocyte Common Antigens / metabolism*
  • Male
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Receptors, Antigen, T-Cell, alpha-beta
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1