Functional significance of adhesion molecules in Fas-dependent apoptotic cell death induced by interleukin-2-activated T cells.
We investigated the functional significance of the adhesion molecules CD2 and lymphocyte function-associated antigen-1 (LFA-1: CD11a/CD18) in Fas-Fas ligand (FasL) death pathway. Interleukin-2-activated T cells expressed a large amount of FasL protein and could efficiently kill a Fas-sensitive leukemic cell line, MML-1. The major part (over 80%) of MML-1 cell death was Fas-dependent. Antibodies to CD2 and CD11a/CD18 completely inhibited MML-1 target cell lysis, whereas effector to target cell binding was partially reduced or not affected at all. These results suggest that effector/target interaction via CD2/CD58 and LFA-1/CD54 systems would be essential for triggering target cell death. More interestingly, there is the discordance in the ability of anti-CD2, and particularly anti-LFA-1 antibodies, to block Fas-dependent cell death versus effector to target conjugate formation. This suggests some non-adhesive role for CD2 and LFA-1 in induction of Fas-dependent cell death. Although these antibodies were capable of inhibiting T cell proliferative response, there was no significant reduction of FasL or granzyme B expression. Thus, the signaling pathway for growth inhibition via CD2 and LFA-1 could not be linked to signaling for FasL and granzyme B expression.
Zhou
Y W
YW
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Komada
Y
Y
Inaba
H
H
Deguchi
T
T
Sugiyama
K
K
Azuma
E
E
Sakurai
M
M
D000911:Antibodies, Monoclonal; D017209:Apoptosis; D018801:CD2 Antigens / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D019014:fas Receptor; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases