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Lack of CD28 expression on HIV‐specific cytotoxic T lymphocytes is associated with disease progression
Author(s) -
Gamberg Jane,
Pardoe Ingrid,
Bowmer M Ian,
Howley Constance,
Grant Michael
Publication year - 2004
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/j.1440-1711.2004.01204.x
Subject(s) - cd28 , ctl* , cytotoxic t cell , cd8 , biology , immunology , population , t cell , cytokine , immune system , medicine , genetics , in vitro , environmental health
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, TCRβV 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 TCRβV 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‐γ, regardless of disease stage and/or the predominant CD28 phenotype of anti‐HIV CTL.