Maintenance of large numbers of virus-specific CD8(+) T cells in HIV-infected progressors and long-term nonprogressors

The virus-specific CD8(+) T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low lev els of plasma viral RNA and strong proliferative responses to HIV Ags, HIV- specific CD8(+) T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis, The frequencies of CD8(+) T cells specific to the majority of HIV gene prod ucts were measured by how cytometric detection of intracellular IFN-gamma i n response to HIV-vaccinia recombinant-infected autologous B cells. Very hi gh frequencies (0.8-18.0%) of circulating CD8(+) T cells were found to be H IV specific. High frequencies of HIV-specific CD8(+) T cells were not limit ed to long-tern nonprogressors with restriction of plasma virus. No correla tion was found between the frequency of HIV-specific CD8(+) T cells and lev els of plasma viremia, In each case, the vast majority of cells (up to 17.2 %) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the major ity of cases not contained within large monoclonal expansions. These data d emonstrate that high numbers of HIV-specific CD8(+) T cells exist even in p atients with high-level viremia and progressive disease. Further, they sugg est that other qualitative parameters of the CD8+ T cell response may diffe rentiate some patients with very low levels of plasma virus and nonprogress ive disease.