Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas.
A number of murine T-cell hybridomas undergo apoptosis within a few hours of activation by specific antigens, mitogens, antibodies against the T-cell antigen receptor, or a combination of phorbol ester and calcium ionophore. This phenomenon has been extensively studied as a model for clonal deletion in the immune system, in which potentially autoreactive T cells eliminate themselves by apoptosis after activation, either in the thymus or in the periphery. Here we show that the Fas/CD95 receptor, which can transduce a potent apoptotic signal when ligand, is rapidly expressed following activation of T-cell hybridomas, as is its functional, membrane-bound ligand. Interference with the ensuing Fas/Fas-ligand interaction inhibits activation-induced apoptosis. Because T-cell receptor ligation can induce apoptosis in a single T hybridoma cell, we suggest that the Fas/Fas-ligand interaction can induce cell death in a cell-autonomous manner.
Brunner
T
T
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, California 92037.
Mogil
R J
RJ
LaFace
D
D
Yoo
N J
NJ
Mahboubi
A
A
Echeverri
F
F
Martin
S J
SJ
Force
W R
WR
Lynch
D H
DH
Ware
C F
CF
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D004247:DNA; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019014:fas Receptor
D000954:Antigens, Surface; D008024:Ligands; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D004247:DNA; D010450:Endopeptidases