Submitted on August 30, 2002
Accepted on April 9, 2003
Fas is Not Essential for Lamina Propria T Lymphocyte Homeostasis
David L. Boone1, Themistocles Dassopoulos1, Sophia Chai1, Marcia Chien1, James Lodolce1, and Averil Ma1*
1 Department of Medicine, IBD Research Center and Committee on Immunology, The University of Chicago, Chicago, IL, USA
* To whom correspondence should be addressed. E-mail: ama{at}medicine.bsd.uchicago.edu.
IL-2 receptor alpha deficient (IL2R
-/-) mice spontaneously accumulate vast numbers of intestinal lamina propria (LP) T cells and develop bowel inflammation. The accumulation of T cells in IL2R-/- 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 IL2R-/- mice, we have directly examined the proliferation and Fas sensitivity of wild-type, lpr/lpr and IL2R-/- LP T cells. In wild-type mice, 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, IL2R-/- mice possess increased total numbers of LP T cells, despite normal proportions of BrdU+ LP T cells. Finally, wild-type and IL2R-/- LP T cells are equivalently Fas sensitive. These results demonstrate that LP T cells proliferate and are Fas sensitive cells. IL2R-/- 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 IL2R-/- mice is independent of defective Fas-induced cell death.
