title: Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms.
abstract: The occurrence, nature, and pathogenesis of intestinal lesions were studied in a number of graft vs. host reaction (GVHR) conditions in mice, combining variations in the nature of the following: the F1 hosts (newborn or adult, normal or lethally irradiated), the injected parental T cells (mixed or selected subsets of Lyt2+ or L3T4+ cells), and the antigenic stimulus (semi-allogeneic or restricted to class I or II MHC loci). The following conclusions were drawn: Three gut alterations are always associated: donor T cell infiltration, predominating in the crypt region; acceleration of the epithelium renewal; and increased epithelial Ia expression. The initial event is T-cell infiltration, which results from stimulation within the Peyer patches followed by cyclic traffic, i.e., migration into the thoracic duct and then seeding to the whole gut mucosa. Both Lyt2+ and L3T4+ cells can infiltrate the gut wall, the extent of the infiltration by a given subset depending upon the capacity of the donor blasts to circulate in the thoracic duct (higher for L3T4+) and then to home in the gut (much higher for Lyt2+ blasts) and the nature of the alloantigenic stimulation that governs the extent of each donor subset proliferation. Both donor T-cell subsets can induce gut epithelial damage, but for a comparable amount of infiltrating cells, L3T4+ cells induce more lesions. When the antigenic stimulation is restricted to class I or class I MHC loci, gut GVHR is much more easily elicited across class II MHC differences, which stimulate preferentially L3T4+ donor cells. The main mechanism of epithelial damage is not direct cytotoxicity, but more probably lymphokine(s) release.
mesh_terms: D000818:Animals; D004848:Epithelium / Q000473:pathology; D006087:Graft vs Host Reaction; D006680:HLA Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D008222:Lymphokines / Q000378:metabolism; D008285:Major Histocompatibility Complex; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000145:classification / Q000473:pathology; D013897:Thoracic Duct / Q000473:pathology
chemical_list: D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D008222:Lymphokines