Functional and phenotypic evidence for a selective loss of memory T cells in asymptomatic human immunodeficiency virus-infected

In addition to a well-documented depletion of CD4 ' T helper cells in later stages of human immunodeficiency virus (HIV) infection, evidence has been provided for a specific unrespon-siveness to triggering either by specific antigen in the context of autologous major histocompatibility molecules (self + X) or anti-CD3 monoclonal antibodies (MAb) in both CD4 and CD8 cells from asymptomatic HIV-infected individuals. In the pres-ent study we analyzed this unresponsiveness using mitogenic antibodies to distinct T cell membrane receptors. T cells from HIV-infected men who had normal numbers of CD4+ T cells responded poorly to activation signals via the CD3 membrane antigen in both accessory cell-dependent as well as accessory cell-independent culture systems. A similar low response was observed in an anti-CD2-driven system. In contrast, prolifera-tion induced by anti-CD3, anti-CD2, or the phorbol ester Phorbol myristate acetate could be normally enhanced by anti-CD28 MAb. We demonstrated that this unresponsiveness is not due to a failure to induce early events required for activa-tion, such as increased intracellular concentration of free cal-cium and activation of protein kinase C, but is caused by an imbalance between naive and memory T cells. In HIV-infected asymptomatic men, CD29 ' memory T cells are selectively de-pleted which results in a poor responsiveness to self + X. These findings provide new insights that may have implica-tions for our understanding of the immunopathogenesis o