Abstract
Progressive HIV disease has been associated with loss of memory T cell responses to Ag. To better characterize and quantify long-lived memory T cells in vivo, we have refined an in vivo labeling technique to study the kinetics of phenotypically distinct, low-frequency CD8(+) T cell subpopulations in humans. HIV-negative subjects and antiretroviral-untreated HIV-infected subjects in varying stages of HIV disease were studied. After labeling the DNA of dividing cells with deuterated water ((2)H(2)O), (2)H-label incorporation and die-away kinetics were quantified using a highly sensitive FACS/mass spectrometric method. Two different populations of long-lived memory CD8(+) T cells were identified in HIV-negative subjects: CD8(+)CD45RA(-)CCR7(+)CD28(+) central memory (T(CM)) cells expressing IL-7Ralpha and CD8(+)CD45RA(+)CCR7(-)CD28(-) RA effector memory (T(EMRA)) cells expressing CD57. In pilot studies in HIV-infected subjects, T(CM) cells appeared to have a shorter half-life and reduced abundance, particularly in those with high viral loads; T(EMRA) cells, by contrast, retained a long half-life and accumulated in the face of progressive HIV disease. These data are consistent with the hypothesis that IL-7Ralpha(+) T(CM) cells represent true memory CD8(+) T cells, the loss of which may be responsible in part for the progressive loss of T cell memory function during progressive HIV infection.