Gut-homing CD4+ T cell receptor alpha beta+ T cells in the pathogenesis of murine inflammatory bowel disease.
We studied which T cell subsets from the gut-associated lymphoid tissue (GALT) can migrate out of the gut mucosa and repopulate GALT compartments of an immunodeficient (semi)syngeneic host. Many distinct lymphocyte subsets were found in GALT of immunocompetent H-2d (BALB/c, BALB/cdm2, C.B-17+/+) mice. No antigen receptor-expressing lymphoid cells were found in GALT of congenic C.B-17 scid/scid (scid) mice. The heterotopic transplantation of a full-thickness gut wall graft from the ileum or colon of immunocompetent (C.B-17+/+, BALB/cdm2) donor mice onto immunodeficient scid mice selectively reconstituted a CD3+ T cell receptor alpha beta+ CD4+ T cell subset. CD4+ cells of this subset expressed the surface phenotype of mucosa-seeking, memory T cells. In the immunodeficient scid host, this gut-derived CD4+ T cell subset was found in spleen, peritoneal cavity, mesenteric lymph nodes (LN), epithelial layer and lamina propria of the small and large intestine, but not in peripheral LN. Scid mice heterotopically transplanted with gut from a congenic, immunocompetent donor developed clinical and histological signs of inflammatory bowel disease (IBD). Hence, the selective repopulation of GALT compartments with CD4+ T cells from normal GALT plays an essential role in the pathogenesis of IBD in an immunodeficient host.
Department of Bacteriology, University of Ulm, FRG.
A
A
Rudolphi
G
G
Boll
S S
SS
Poulsen
M H
MH
Claesson
J
J
Reimann
D000818:Animals; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D016219:Immunotherapy, Adoptive; D015212:Inflammatory Bowel Diseases / Q000209:etiology* / Q000276:immunology; D007422:Intestines / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*
D017252:CD3 Complex; D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta