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INFLAMMATION/IMMUNITY/MEDIATORS
Department of Medicine, Inflammatory Bowel Disease Research Center and Committee on Immunology, The University of Chicago, Chicago, Illinois 60637
Submitted 30 August 2002 ; accepted in final form 9 April 2003
IL-2 receptor
-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,
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, 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.
intestinal inflammation; colitis
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