Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: Correlation with disease progression

Few studies have examined longitudinal changes in human immunodeficiency vi rus type 1 (HIV)-specific cytotoxic T lymphocytes (CTL). To more closely de fine the natural history of HIV-specific CTL, we used HLA-peptide tetrameri c complexes to study the longitudinal CD8(+) T-cell response evolution in 1 6 A*0201-positive untreated individuals followed clinically for up to 14 ye ars. As early as 1 to 2 years after seroconversion, we found a significant association between high frequencies of A*0201-restricted p17(Gag/Pol) tetr amer-binding cells and slower disease progression (P < 0.01). We observed t hat responses could remain stable over many months, but any longitudinal ch anges that occurred were typically accompanied by reciprocal changes in RNA viral load. Phenotypic analysis with markers CD45RO, CD45RA, and CD27 iden tified distinct subsets of antigen-specific cells and the preferential loss of CD27(+) CD45RO(+) cells during periods of rapid decline in the frequenc y of tetramer-binding cells. Pn addition we were unable to confirm previous studies showing a consistent selective loss of HIV-specific cells in the c ontext of sustained Epstein-Barr virus-specific cell frequencies. Overall, these data support a role of HIV-specific CTL in the control of disease pro gression and suggest that the ultimate loss of such CTL may be preferential ly from the CD27(+) CD45RO(+) subset.