Evidence that Ia+ bone-marrow-derived cells are the stimulus for the intestinal phase of the murine graft-versus-host reaction.

We have investigated whether bone marrow (BM) or tissue-derived cells provide the stimulus for the intestinal phase of graft-versus-host reaction (GVHR) in F1 mice injected with parental spleen cells. After injection of CBA cells, the characteristic increases in crypt length, crypt cell production rate (CCPR), and intraepithelial lymphocyte (IEL) count occurred in the jejunum of (CBA x BALB/c)F1----CBA BM chimeras, but not in CBA----(CBA x BALB/c)F1 BM chimeras. Thus, BM-derived cells alone can induce intestinal GVHR and, as similar intestinal alterations were found in (A.TH x A.TL)----A.TL BM chimeric mice after injection of A.TL spleen cells, we deduce that the BM-derived stimulator cells are Ia+. We conclude that the intestinal pathology in this model of GVHR is an indirect effect of soluble mediators that are released during a local delayed-type hypersensitivity (DTH) reaction induced by recognition of Ia+ passenger leukocytes within the mucosa.