title: 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.
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.
authors.affiliation: Department of Pediatrics, Division of Immunology and Infectious Diseases, University of Florida, College of Medicine, Gainesville, Florida, USA.
authors.forename: Zhong Chen
authors.initials: ZC
authors.lastname: Kou
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Puhr
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Wu
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
authors.forename: John W
authors.initials: JW
authors.lastname: Sleasman
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002648:Child; D005260:Female; D005786:Gene Expression Regulation; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000378:metabolism*; D008297:Male; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1