CD2 rescues T cells from T-cell receptor/CD3 apoptosis: a role for the Fas/Fas-L system.
Anti-CD3 monoclonal antibodies (MoAbs) and glucocorticoid hormones induce apoptosis in immature thymocytes and peripheral T lymphocytes. This process is inhibited by a number of growth factors, including interleukin-2 (IL-2), IL-3, and IL-4, as well as by triggering of the adhesion molecule CD44, which would indicate that signals generated by membrane receptors can modulate the survival of lymphoid cells. To investigate whether triggering of CD2 may also affect apoptosis in lymphoid cells, we analyzed the effect of stimulation with anti-CD2 MoAbs on T-cell apoptosis induced by two stimuli, anti-CD3 MoAbs and dexamethasone (DEX), using a hybridoma T-cell line and a T-helper cell clone. The results show that CD2 engagement decreased anti-CD3 MoAb-induced apoptosis, but did not influence DEX-induced cell death. Furthermore, the decrease appeared to be related to the expression of Fas/APO-1 (CD95) and Fas-ligand (Fas-L). In fact, we show that CD2 stimulation inhibits apoptosis by preventing the CD3-induced upregulation of Fas and Fas-L in a Fas-dependent experimental system. These data suggest that a costimulatory molecule may control a deletion pathway and may therefore contribute to the regulation of peripheral tolerance.
Ayroldi
E
E
Department of Clinical Medicine, Pathology, and Pharmacology, Perugia University, Medical School, Italy.
Migliorati
G
G
Cannarile
L
L
Moraca
R
R
Delfino
D V
DV
Riccardi
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018801:CD2 Antigens / Q000276:immunology / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D003907:Dexamethasone / Q000494:pharmacology; D053222:Fas Ligand Protein; D006825:Hybridomas / Q000166:cytology / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D016853:Muromonab-CD3 / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019014:fas Receptor; D003907:Dexamethasone