A unique subset of self-specific intraintestinal T cells maintains gut integrity.
Lymphocytes residing in the intestinal epithelium are exclusively T cells and account for one of the largest collection of T cells in the organism. However, their function remains obscure. We and others have shown that the development of intestinal intraepithelial T cells is compromised in mutant mice prone to chronic intestinal inflammation. These results led us to directly assess their role in regulating the development of colitis secondary to transfer of primary splenic TCRalphabeta(+)CD4(+)CD45RB(hi) T cells into severe combined immunodeficiency (SCID) mice. Here we demonstrate that prior reconstitution of SCID recipients with intraintestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells prevents disease, and does so in an interleukin (IL)-10-dependent fashion. In contrast, reconstitution with either TCRgammadelta(+) or TCRalphabeta(+)CD4(-) CD8alpha(+)beta(+) intestinal T cells did not prevent colitis. TCRalphabeta(+)CD4(-)8alpha(+)beta(-) T cells are unique to the intestinal epithelium of both rodents and humans. Previous repertoire analyses of TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells revealed a high proportion of cells expressing high affinity, self-specific TCR within this subset. We demonstrate that monoclonal, self specific TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) cells derived from TCR transgenic mice also prevent the onset of colitis. Thus, intestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells, selected based on their self-reactivity, maintain gut integrity in a IL-10-dependent fashion.
Poussier
Philippe
P
Sunnybrook and Women's Health Sciences Centre, 2075 Bayview Avenue, Room A3 38, Toronto, Ontario M4N 3M5, Canada. ppoussie@sten.sunnybrook.utoronto.ca
Ning
Terri
T
Banerjee
Diponkar
D
Julius
Michael
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000166:cytology / Q000502:physiology*
D016753:Interleukin-10