EFFECT OF CHRONIC GRAFT-VERSUS-HOST DISEASE ON THE INTESTINE IN ADULT BDF1 MICE

This study was performed to characterize the intestinal lesions in chronic graft-versus-host disease (GVHD) in mice and to determine a possible role of intestinal intraepithelial lymphocytes (ilEL) in the development of these lesions. Chronic GVHD was induced by transfer of DBA/2 lymphocytes into non-irradiated (C57BL/10 x DBA/2)F1 (BDF1) recipients. There was mild to moderate mucosal oedema with multifocal mixed inflammatory cell infiltrations in the small intestine. The caecum was more severely affected with severe oedema, progressive loss of crypts and severe distortion of the mucosal architecture. The total number of ilEL did not change during the development of chronic GVHD, but there were alterations in the composition of the ilEL population. An increase of CD3+, Thy-1+ cells was accompanied by an increase of TCRalphabeta+ cells and a decrease of TCRgammadelta+ cells. There was no evidence of infiltration of donor lymphocytes into the intestinal epithelium as determined by the H2K haplotype of the ilEL. These lesions differ from previously described models of chronic GVHD, induced by DBA/2 donor lymphocytes in BDF1 recipients. We suggest that the haemopoietic organs that are used as the source of donor lymphocytes determine the outcome of the GVHD. Modulation of the composition of the donor lymphocyte population may be useful in the establishment of relevant animal models of human enteropathy.