Expression and function of mouse Fas antigen on immature and mature T cells.
We prepared mAbs specific for the mouse Fas Ag (CD95) and used them to analyze the expression and apoptosis-inducing activity of the Fas Ag on murine immunocytes. Cytofluorometry of mouse bone marrow, thymus, and splenocytes using the mAbs indicated that cells of the T lineage, except for bone marrow cells, expressed Fas Ag on the surface. CD4-CD8- undifferentiated thymocytes expressed low levels of Fas Ag. Immature CD4+CD8+ thymocytes and mature CD4+CD8- and CD4-CD8+ thymocytes were highly positive for Fas Ag. CD4+CD8+ thymocytes were specifically sensitive to the apoptosis-inducing activity of anti-Fas, although CD4-CD8-, CD4+CD8-, and CD4-CD8+ thymocytes were resistant. Spleen T cells were resistant to anti-Fas, whereas they expressed Fas Ag. The superantigen, staphylococcal enterotoxin B (SEB) administered to BALB/c mice, induced clonal expansion and successive clonal deletion of spleen T cells bearing the V beta 8 TCR, which specifically reacts to SEB. Such clonal deletion of V beta 8 T cells was highly suppressed in lpr mice, which have defects in the Fas Ag gene. In SEB-administrated BALB/c mice, expression of Fas Ag was significantly enhanced on V beta 8, but not on V beta 6 T cells, which cannot react to SEB. Moreover, V beta 8 T cells in SEB-primed mice were sensitive to the cell-killing activity of anti-Fas, although V beta 6 T cells were resistant. These findings show that the expression level and apoptosis-inducing activity of Fas Ag on peripheral T cells are directly up-regulated by stimulation through the TCR in vivo.
Nishimura
Y
Y
Pharmaceutical Basic Research Laboratories, JT Inc., Yokohama, Japan.
Ishii
A
A
Kobayashi
Y
Y
Yamasaki
Y
Y
Yonehara
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology; D006224:Cricetinae; D003412:Cricetulus; D004768:Enterotoxins / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D011233:Precipitin Tests; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D019014:fas Receptor
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D004768:Enterotoxins; D011994:Recombinant Proteins; D018089:Superantigens; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal