Apoptotic features of peripheral blood granulocytes and monocytes during primary, acute HIV infection.

Apoptosis plays a major role during HIV infection, including the primary, acute HIV syndrome (AHS), during which such phenomenon is massive. We asked whether apoptosis involved not only peripheral blood lymphocytes, but also monocytes (PBM) and granulocytes (PBG). Thus, we studied cells from different patients during the acute phase of the viral syndrome. The CD95 molecule was expressed at high density on the PBM and PBG surface during AHS. Culturing PBG for a few hours resulted in a significant membrane expression of phosphatidylserine, consistent with apoptosis. However, cells maintained for hours plasma membrane integrity and showed no relevant changes in mitochondrial membrane potential. The overexpression of CD95 was not associated with high plasmatic levels of sCD95 and, together with apoptosis and its related markers decreased after a few weeks of highly active antiretroviral therapy. During AHS, a deregulation of the CD95 system occurs in monocytes and granulocytes, is related to a high propensity of PBG to undergo apoptosis, and may contribute to the pathogenesis of the disease. Antiretroviral treatment resulted not only in a decrease of virus production, but also in a reduced PBG tendency to undergo spontaneous apoptosis. Even if the mechanism(s) responsible for this phenomenon remains to be elucidated, our data suggest a possible (indirect?) action of antiretroviral therapies on PBG and PBM which could explain, at least partially, the rescue of natural immunity and the reduced use of granulocyte-colony stimulating factor during such treatments.