Fas is not essential for lamina propria T lymphocyte homeostasis.
IL-2 receptor alpha-deficient (IL2Ralpha-/-) mice spontaneously accumulate vast numbers of intestinal lamina propria (LP) T cells and develop bowel inflammation. The accumulation of T cells in IL2Ralpha-/- 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 IL2Ralpha-/- mice, we have directly examined the proliferation and Fas sensitivity of wild-type, lpr/lpr, and IL2Ralpha-/- 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, IL2Ralpha-/- mice possess increased total numbers of LP T cells, despite normal proportions of BrdU+ LP T cells. Finally, wild-type and IL2Ralpha-/- LP T cells are equivalently Fas sensitive. These results demonstrate that LP T cells proliferate and are Fas-sensitive cells. IL2Ralpha-/- 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 IL2Ralpha-/- mice is independent of defective Fas-induced cell death.
Boone
David L
DL
Department of Medicine, Inflammatory Bowel Disease Research Center, Committee on Immunology, The University of Chicago, IL 60637, USA.
Dassopoulos
Themistocles
T
Chai
Sophia
S
Chien
Marcia
M
Lodolce
James
J
Ma
Averil
A
D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D006706:Homeostasis; D018960:Hyaluronan Receptors / Q000032:analysis; D006984:Hypertrophy; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D013934:Thymectomy; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2; D019014:fas Receptor; D001973:Bromodeoxyuridine