Fas is not essential for lamina propria T lymphocyte homeostasis

Abstract

IL-2 receptor α-deficient (IL2Rα-/-) mice spontaneously accumulate vast numbers of intestinal lamina propria (LP) T cells and develop bowel inflammation. The accumulation of T cells in IL2Rα-/- mice is thought to result, in part, from defective Fas-induced cell death. To understand the role of cell proliferation and death in regulating LP T cells in IL2Rα-/- mice, we have directly examined the proliferation and Fas sensitivity of wild-type, lpr/lpr, and IL2Rα-/- LP T cells. In wild-type mice, 5′-bromodeoxyuridine (BrdU) labeling and Fas susceptibility are greatest in CD44Hi LP T cells. Fas-deficient lpr/lpr mice have normal total numbers of LP T cells, despite an increased proportion of BrdU+ T cells. By contrast, IL2Rα-/- mice possess increased total numbers of LP T cells, despite normal proportions of BrdU+ LP T cells. Finally, wild-type and IL2Rα-/- LP T cells are equivalently Fas sensitive. These results demonstrate that LP T cells proliferate and are Fas-sensitive cells. IL2Rα-/- mice accumulate a large number of these Fas-sensitive LP T cells and clearly differ from Fas-deficient lpr/lpr mice in this regard. Thus our studies reveal that Fas is dispensable for LP T cell homeostasis and suggest that the intestinal inflammation observed in IL2Rα-/- mice is independent of defective Fas-induced cell death.