Induction of CD95 ligand expression on T lymphocytes and B lymphocytes and its contribution to apoptosis of CD95-up-regulated CD4+ T lymphocytes in macaques by infection with a pathogenic simian/human immunodeficiency virus

Using an established SIV/HIV-C2/1-infected cynomolgus monkey model displaying stable CD4(+) T cell depletion, the kinetics of apoptosis and the levels of expression of CD95 membrane-associated CD95L on lymphocytes were investigated to test the involvement of the CD95/CD95L system in CD4(+) T lymphocyte loss in vivo. Rapid depletion of CD4(+) T cells occurred up to 2 weeks after infection, with chronic CD4(+) T lymphopenia thereafter. During the initial CD4(+) T cell loss, which was accompanied by viraemia, about 90% of the peripheral CD4(+) T cell subset underwent spontaneous apoptotic cell death during 24 h of culture. Increased expression of CD95 was observed on both CD4(+) and CD8(+) T cell subsets, with CD95 expression on CD8(+) cells declining rapidly, but high CD95 expression being maintained on CD4(+) cells. Since CD95L was expressed on CD8(+) T cells, B cells and to a lesser extent on CD4(+) T cells, this suggests that CD95-mediated apoptosis might be controlled in an autocrine/paracrine fashion.