Memory CD4+ T-cells in HIV-Infected Immunological Nonresponders are Prone to Apoptosis When Cycling

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Immunological nonresponders (INRs) are HIV-infected patients that poorly restore CD4+ T-cell counts despite the efficient viral suppression upon highly active antiretroviral therapy. In INRs blood, the frequency of T-helper cells entering the cell division cycle is increased. Nevertheless, no efficient CD4+ T-lymphocyte gain is observed. The aim of the present study was to investigate the viability of cycling CD4+ T-cells received from INRs. Fifty seven subjects were studied: INRs (n = 16), immunological responders (IRs; n = 21); healthy controls (n = 20). Cycling (CD71+) and resting (CD71–) naive and memory CD4+ T-cells were analyzed by flow cytometry. Their apoptotic gene profile was studied with the microarray technique. It was shown that in INRs, the majority of cells involved in lymphopenia-induced proliferation are memory CD4+ T-lymphocytes. These cells exhibit a pro-apoptotic gene expression profile. And their apoptosis indices are negatively correlated with the peripheral CD4+ T-cell counts in HIV-positive subjects. Thus in INRs, homeostatic proliferation of memory CD4+ T-lymphocytes is initiated as a mechanism to restore the T-helper pool size. But unlike IRs, INRs do not overcome the immunodeficiency due to the extensive apoptosis of memory CD4+ T-cells that enter the cell division cycle.