Apoptosis of human T-cells: induction by glucocorticoids or surface receptor ligation in vitro and ex vivo

Activated T-cells are susceptible to induction of apoptosis or programmed c ell death in response to ligation of several cell surface structures, inclu ding CD2, CD3, and CD95/Fas. These mechanisms may be important in the regul ation of immune responses and in prevention of autoimmunity. We used flow c ytometric quantitation of DNA strand breaks to detect T-cells committed to programmed cell death. Activated human peripheral blood T-lymphocytes, and freshly isolated human thymocytes underwent apoptosis when exposed to dexam ethasone or to monoclonal antibodies directed at CD2 or CD3. Interleukin-2 reduced spontaneous or dexamethasone-induced apoptosis, but augmented apopt osis due to ligation of CD2. A neutralizing anti-fas antibody reduced the a mount of DNA strand breakage, not only in T-cells exposed to antibodies to CD2 or CD3, but also in dexamethasone-treated cultures. In vivo activated T-cells, from inflammatory synovial fluids, were sensitiv e to immediate induction of DNA strand breaks without prior in vitro activa tion by lectin and IL-2. Taken together, the results indicated that: 1. Human lymphocytes, like murine thymocytes, are sensitive to glucocortico id-induced apoptosis, as well as to programmed cell death triggered through surface receptors; 2. The effects of IL-2 on T-cell apoptosis depend on the apoptotic stimulus ; 3. Fas/Fas ligand interactions may be relevant for both membrane receptor a nd glucocorticoid-induced cell death; and 4. Induction of T-cell apoptosis may be important in therapeutic effects of glucocorticoids in human disease.