Loss of CD4(+) T cell proliferative ability but not loss of human immunodeficiency virus type 1 specificity equates with progression to disease

In this study, we compared human immunodeficiency virus (HIV) type 1-specif ic proliferative responses with HIV-1-induced intracellular cytokine produc tion in a cohort of clinically nonprogressing patients and individuals with progressive HIV-1 infection. We found strong HIV-1-specific proliferative responses in the clinical nonprogressor cohort that correlated with signifi cant numbers of circulating HIV-1-specific CD4(+) T cells. In contrast, HIV -1-specific proliferative responses were absent in most individuals with pr ogressive HIV-1 infection, even though interferon-gamma-producing HIV-1-spe cific CD4(+) T cells were detectable by flow cytometry. The implication of these data is that the important dysfunction seen in most HIV-positive pati ents from very early in disease may be an inability of HIV-1-specific CD4() memory T cells to proliferate in response to HIV antigens rather than an absolute loss of circulating virus-specific CD4(+) T cells.