title: Apoptosis of human T-cells: induction by glucocorticoids or surface receptor ligation in vitro and ex vivo.
abstract: Activated T-cells are susceptible to induction of apoptosis or programmed cell death in response to ligation of several cell surface structures, including CD2, CD3, and CD95/Fas. These mechanisms may be important in the regulation of immune responses and in prevention of autoimmunity. We used flow cytometric 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 dexamethasone or to monoclonal antibodies directed at CD2 or CD3. Interleukin-2 reduced spontaneous or dexamethasone-induced apoptosis, but augmented apoptosis due to ligation of CD2. A neutralizing anti-Fas antibody reduced the amount 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 sensitive to immediate induction of DNA strand breaks without prior in vitro activation by lectin and IL-2. Taken together, the results indicated that: 1. Human lymphocytes, like murine thymocytes, are sensitive to glucocorticoid-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 and glucocorticoid-induced cell death; and 4. Induction of T-cell apoptosis may be important in therapeutic effects of glucocorticoids in human disease.
authors.affiliation: Department of Internal Medicine, University of Michigan Multipurpose Arthritis and Musculoskeletal Diseases Center, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Kirsch
authors.forename: A A
authors.initials: AA
authors.lastname: Mahmood
authors.forename: J
authors.initials: J
authors.lastname: Endres
authors.forename: L
authors.initials: L
authors.lastname: Bohra
authors.forename: B
authors.initials: B
authors.lastname: Bonish
authors.forename: K
authors.initials: K
authors.lastname: Weber
authors.forename: D A
authors.initials: DA
authors.lastname: Fox
mesh_terms: D000287:Administration, Topical; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000473:pathology; D018801:CD2 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D019070:Cell Lineage; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D017252:CD3 Complex; D005938:Glucocorticoids; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D019014:fas Receptor; D003907:Dexamethasone