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.