Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients.
Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
Aranda
R
R
Department of Gastroenterology, West Los Angeles Veterans Administration Medical Center, CA 90073, USA.
Sydora
B C
BC
McAllister
P L
PL
Binder
S W
SW
Yang
H Y
HY
Targan
S R
SR
Kronenberg
M
M
D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000008:administration & dosage*; D016827:CD8 Antigens / Q000008:administration & dosage; D002465:Cell Movement / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D007420:Intestine, Large / Q000473:pathology; D017493:Leukocyte Common Antigens / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation*
D015704:CD4 Antigens; D016827:CD8 Antigens; D017493:Leukocyte Common Antigens