A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice.
Fas (CD95) and its ligand are central regulatory molecules in hematopoietic cells. Previous studies have suggested a role for Fas in the regulation of tumor progression, but Fas has not yet been conclusively identified as a tumor suppressor. Fas-deficient individuals lack malignant tumors, perhaps because of regulation by T cells. To investigate such a possibility, mice deficient in both T cells and Fas were generated, and they were found to develop severe B cell dysregulation characterized by malignant, lethal B cell lymphoma. Lymphoma arose from a monoclonal B220+CD19-CD5-CD23- B cell secreting immunoglobulin M, kappa rheumatoid factor. In contrast, animals containing alpha beta T cells, gamma delta T cells, and/or functional Fas suppressed the development of lymphoma. These data indicate that Fas functions as a tumor suppressor, and identifies roles for both alpha beta T cells and gamma delta T cells in Fas-independent tumor regulation.
Peng
S L
SL
Section of Rheumatology, Yale University School of Medicine, New Haven, Connecticut, USA.
Robert
M E
ME
Hayday
A C
AC
Craft
J
J
D000818:Animals; D005260:Female; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D019014:fas Receptor