GUT-HOMING CD4(-CELL RECEPTOR ALPHA-BETA(+) T-CELLS IN THE PATHOGENESIS OF MURINE INFLAMMATORY BOWEL-DISEASE() T)

We studied which T cell subsets from the gut-associated lymphoid tissu e (GALT) can migrate out of the gut mucosa and repopulate GALT compart ments of an immunodeficient (semi)syngeneic host. Many distinct lympho cyte subsets were found in GALT of immunocompetent H-2(d) (BALB/c, BAL B/c(dm2), C.B-17+/+) mice. No antigen receptor-expressing lymphoid cel ls were found in GALT of congenic C.B-17 scid/scid (scid) mice. The he terotopic transplantation of a full-thickness gut wall graft from the ileum or colon of immunocompetent (C.B-17+/+, BALB/c(dm2)) donor mice onto immunodeficient scid mice selectively reconstituted a CD3(+) T ce ll receptor alpha beta(+) CD4(+) T cell subset. CD4(+) cells of this s ubset expressed the surface phenotype of mucosa-seeking, memory T cell s. In the immunodeficient scid host, this gut-derived CD4(+) T cell su bset was found in spleen, peritoneal cavity, mesenteric lymph nodes (L N), epithelial layer and lamina propria of the small and large intesti ne, but not in peripheral LN. Scid mice heterotopically transplanted w ith gut from a congenic, immunocompetent donor developed clinical and histological signs of inflammatory bowel disease (IBD). Hence, the sel ective repopulation of GALT compartments with CD4(+) T cells from norm al GALT plays an essential role in the pathogenesis of IBD in an immun odeficient host.