Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses?
Fas/Fas ligand interactions serve as a signaling pathway for apoptosis (1-3), an important regulatory mechanism in the development and function of the immune system (4-9). Recent evidence that Fas-dependent apoptosis is also an important mode of T cell cytotoxicity (10-13) suggested that Fas might play a critical role in the effector phase of T-dependent immune responses, such as allograft rejection. We observed that Fas transcripts are constitutively expressed in syngeneic and allogeneic murine cardiac transplants, while Fas ligand (FasL) is up-regulated only in rejecting allografts. Surprisingly, the absence of an intact Fas/FasL pathway did not alter the tempo of allograft rejection, even CD4-dependent rejection. These results indicate that Fas/FasL interactions are not essential mediators of T cell-induced allograft damage. Rather, as suggested in other studies, the Fas pathway may be principally involved in the regulation of clonal expansion and subsequent contraction of T cell populations during immune responses.
Larsen
C P
CP
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Alexander
D Z
DZ
Hendrix
R
R
Ritchie
S C
SC
Pearson
T C
TC
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D016923:Cell Death / Q000502:physiology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor
D000954:Antigens, Surface; D015704:CD4 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor