MEMBRANE AND SOLUBLE FORMS OF FAS (CD95) AND FAS LIGAND IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND IN PLASMA FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PERSONS

The expression of membrane-bound Fas ligand (FasL) and Fas in lymphocy tes and monocytes and levels of soluble forms of Fast (sFasL) and Fas (sFas) in plasma from human immunodeficiency virus (HIV)-positive and -negative subjects was evaluated. Surface Fast was detectable on monoc ytes, but poorly so on lymphocytes, even in the presence of KB8301, a metalloproteinase inhibitor. Unexpectedly, monocytes of HIV-positive s ubjects expressed less Fast than those of HN-negative volunteers. sFas L levels in plasma of HIV-positive persons were elevated and correlate d with levels in plasma and with HIV RNA burden. sFas levels in plasma of HIV-positive subjects were also elevated and correlated with Fas e xpression in apoptotic lymphocytes. Finally, culture-induced lymphocyt e apoptosis of HIV-positive subjects was enhanced by anti-Fas agonisti c antibody but was not inhibited by anti-Fast blocking antibodies. The se results suggest that significant dysregulation of both Fas and Fast occurs in HN infection and contributes to increased sensitivity of ly mphocytes to apoptosis.