A TUMOR-SUPPRESSOR FUNCTION FOR FAS (CD95) REVEALED IN T-CELL-DEFICIENT MICE

Fas (CD95) and its ligand are central regulatory molecules in hematopo ietic cells. Previous studies have suggested a role for Fas in the reg ulation of tumor progression, but Fas has not yet been conclusively id entified as a tumor suppressor. Fas-deficient individuals lack maligna nt tumors, perhaps because of regulation by T cells. To investigate su ch a possibility, mice deficient in both T cells and Fas were generate d, and they were found to develop severe B cell dysregulation characte rized by malignant, lethal B cell lymphoma. Lymphoma arose from a mono clonal 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 devel opment 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.