An activated CD8+ T cell phenotype correlates with anti-HIV activity and asymptomatic clinical status.

We have examined the relation of cell surface marker phenotype to the anti-human immunodeficiency virus (HIV) function of CD8+ cells from individuals at various clinical stages of HIV infection. Multiparametric flow cytometry analysis demonstrated that the most significant changes in cell surface phenotype was found within the CD8+ cell subset expressing HLA-DR and CD28. These changes in the levels of CD28 and HLA-DR expression on CD8+ cells were found to be related to antiviral activity and have clinical relevance based on three pieces of evidence: (1) strong CD8+ cell antiviral responses were associated in infected individuals with high levels of HLA-DR+ and CD28+ subsets; (2) CD8+ cell anti-HIV activity in vitro resides predominantly in the separated CD8+ cell subsets that express HLA-DR or CD28; and (3) in longitudinal studies, CD8+ cell anti-HIV activity decreased as an individual progressed from a healthy state to an AIDS condition. Taken together, the data suggest that the CD8+ cell subset identified phenotypically as a CD8+ CD28+ HLA-DR+ cell is responsible for natural anti-HIV activity. Longitudinal studies should determine if alterations in this subset can be used as a prognostic indicator for disease progression.