1. ¹Immunology Program, Division of Basic Medical Science, Faculty of Medicine, Memorial University of Newfoundland, St. Johns, NL, Canada
2. ²Health Care Corporation of St. John's, St. John's, NL, Canada

Correspondence: Dr M. Grant, H1809-Immunology, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. Johns, NL, Canada A1B 3V6. Email: mgrant@mun.ca

Received 29 July 2003; Accepted 13 October 2003.

Abstract

During HIV infection, CD8⁺ T cells lacking the costimulatory molecule CD28 increase in number and proportion. This accumulation is associated with disease activity and possibly with CD8⁺ T-cell dysfunction. In this study, CD8⁺CD28⁺ and CD8⁺CD28^- T cells from 41 HIV-infected individuals at various stages of disease were compared in terms of HIV-specific cytotoxicity, TCRV repertoire diversity, and cytokine production. We found that the CD28 phenotype of anti-HIV CTL evolves in parallel with disease progression and disease activity. Absolute numbers of CD4⁺ T cells and CD4⁺/CD8⁺ T-cell ratios progressively decreased in 3 groups with an increasing prevalence of CD28^- HIV-specific CTL. Conversely, HIV replication levels progressively increased in parallel with the prevalence of CD28^- HIV-specific CTL. Repertoire diversity at the level of TCRV gene family expression was maintained at normal levels for both CD28⁺ and CD28^- T cells at all stages of infection. Diversity at the level of junctional length polymorphism was more restricted in the CD8⁺CD28^- T-cell population, but this difference remained relatively constant through different stages of infection. Both CD28⁺ and CD28^- T cells produced IL-2 and IFN-, regardless of disease stage and/or the predominant CD28 phenotype of anti-HIV CTL.