Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-γ+ HIV-specific T cells during progression to AIDS

Although CD8(+) T cells initially suppress human immunodeficiency virus (HIV) replication, cytotoxic T-cell precursor frequencies eventually decline and fall to prevent disease progression. In a longitudinal study including 16 individuals infected with HIV-1 we studied both the number and function of HIV-specific CD8(+) T cells by comparing HLA-peptide tetramer staining and peptide-induced interferon-gamma (IFN-gamma), production. Numbers of IFN-gamma-producing T cells declined during progression to acquired immunodeficiency, syndrome (AIDS), whereas the number of tetramer(+) T cells: in many individuals persisted at high frequencies. Loss of IFN-gamma-producing T cells correlated with declining CD4(+) T-cell counts, consistent with the need of CD4(+) T-cell help in maintaining adequate CD8(+) T-cell function. These data indicate that the loss of HIV-specific CD8(+) T-cell activity is not due to physical depletion, but is mainly due to progressively impaired function of HIV-specific CD8(+) T cells. (C) 2002 by The American Society of Hematology.