Interleukin-6 (IL-6) prevents activation-induced cell death: IL-2-independent inhibition of Fas/fasL expression and cell death.
Triggering of the TCR/CD3 complex with specific antigen or anti-CD3 monoclonal antibody initiates activation-induced cell death (AICD) in mature T cells, an effect also mediated by the Fas/FasL system. We have previously shown that CD2 stimulation rescues T cells from TCR/CD3-induced apoptosis by decreasing the expression of Fas and FasL. In the present study, we examined whether the endogenous production of IL-2 plays a role in the effects mediated by CD2 triggering. The results indicated that transcription of Fas/FasL is controlled by interleukin-2 (IL-2) production and that CD2 triggering rescues a T-cell hybridoma from AICD via decreased production of IL-2. To ascertain whether modulation of IL-2 may be a general mechanism of AICD control, we examined other stimuli, capable of modulating the expression of the Fas/FasL system and the ensuing AICD, for ability to affect production of IL-2. We found that IL-6 reduced the level of TCR/CD3-induced apoptosis and the expression of Fas/FasL, yet failed to inhibit IL-2 production. Because IL-2 is involved in both apoptosis and activation events, these results indicate that, in contrast to CD2, which inhibits apoptosis and T cell activation, IL-6 inhibits apoptosis but not IL-2-induced activation. These observations may provide the basis for differential control of T-cell activation and apoptosis.
Ayroldi
E
E
Pharmacology Section, the Department of Clinical and Experimental Medicine and the Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Zollo
O
O
Cannarile
L
L
D' Adamio
F
F
Grohmann
U
U
Delfino
D V
DV
Riccardi
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D006224:Cricetinae; D015536:Down-Regulation; D053222:Fas Ligand Protein; D007376:Interleukin-2 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019014:fas Receptor