CD4(-LYMPHOCYTES INJECTED INTO SEVERE COMBINED IMMUNODEFICIENT (SCID)MICE LEAD TO AN INFLAMMATORY AND LETHAL BOWEL-DISEASE() T)

Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alpha bet a(+) CD4(+) T cells to SCID mice leads to an infiltration of the recip ient gut lamina propria and epithelium with a donor-derived CD4(+) T c ell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients. In contrast, IBD was not observed in SCID mice transpl anted with unfractionated splenic cells. The earliest detectable patho logical changes after CD4(+) T cell transfer were proliferation and hy pertrophy of the entire colonic epithelial layer, including increased mitotic activity, increased expression of epithelial nuclear prolifera tion antigen, and elongation of the crypts. Later on, massive mononucl ear cell infiltration, hypertrophy of all layers of the colon and occa sional epithelial ulcerations were observed. At this stage, accumulati ons of IgA, IgM and small numbers of IgG1-, IgG2- and IgG3-secreting p lasma cells were present in the lamina propria of both the small and l arge intestine. We conclude that low numbers of intraveneously transfe rred CD4(+) T cells induce IBD in SCID mice. In the late stages of CD4 (+) T cell-induced IBD, the colonic lamina propria becomes infiltrated with macrophages, neutrophils and plasma cells secreting IgA, IgM, an d to a lesser degree IgG antibodies which might play an accessory role in the pathogenesis of IBD.