IN-VIVO ANALYSIS OF FAS FASL INTERACTIONS IN HIV-INFECTED PATIENTS/

Recent insights into the pharmacological control of HIV replication an d the molecular mechanisms of peripheral T cells homeostasis allowed u s to investigate in vivo the mechanisms mediating T cell depletion in HIV-infected patients. Before the initiation of highly active antiretr oviral therapy (HAART), a high degree of lymphoid tissue apoptosis is present, which is reduced upon HAART initiation (P < 0.001) and direct ly correlates with reduction of viral load and increases of peripheral T lymphocytes (P < 0.01), Because Fas/FasL interactions play a key ro le in peripheral T lymphocyte homeostasis, we investigated the suscept ibility to Fas-mediated apoptosis in peripheral T lymphocytes and of F ast expression in lymphoid tissue before and during HAART, High levels of Fas-susceptibility found in peripheral CD4 T lymphocytes before HA ART were significantly reduced after HAART, coinciding with decreases in viral load (P = 0.018) and increases in peripheral CD4 T lymphocyte counts (P < 0,01), However, the increased Fast expression in the lymp hoid tissue of HIV-infected individuals was not reduced after HAART. T hese results demonstrate that lymphoid tissue apoptosis directly corre lates with viral load and peripheral T lymphocyte numbers, and suggest that HIV-induced susceptibility to Fas-dependent apoptosis may play a key role in the regulation of T cell homeostasis in HIV-infected indi viduals.