Lack of CD28 expression on HIV-specific cytotoxic T lymphocytes is associated with disease progression.
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, TCR beta V 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 TCR beta V 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-gamma, regardless of disease stage and/or the predominant CD28 phenotype of anti-HIV CTL.
Gamberg
Jane
J
Immunology Program, Division of Basic Medical Science, Faculty of Medicine, Memorial University of Newfoundland, St. John's NL, Canada.
Pardoe
Ingrid
I
Bowmer
M Ian
MI
Howley
Constance
C
Grant
Michael
M
D018106:CD28 Antigens / Q000378:metabolism*; D018450:Disease Progression; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*
D018106:CD28 Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D007371:Interferon-gamma