Ductal lesions of exocrine glands and insulitis induced by L3T4+ T cells following graft-versus-host reaction due to major histocompatibility complex class II disparity.

Recently, we have demonstrated characteristic hepatic lesions resembling primary biliary cirrhosis (PBC) in semiallogeneic F1 hybrid mice with major histocompatibility complex (MHC) class II-disparate graft-versus-host reaction (GVHR). In the present study, we tried to reveal other ductal lesions in extrahepatic organs, including salivary glands and pancreas. Murine strains used are C57BL/6 (B6), B6 mutant bm1, and bm12. bm1 carries a mutant gene at the H-2K locus of MHC and bm12 carries a mutant gene at the I-A locus of MHC of the B6 strain. The (B6 x bm1)F1, (B6 x bm12)F1, and (bm1 x bm12)F1 mice were injected intravenously with 1 x 10(7) B6 L3T4+ or Lyt-2+ T cells and were sacrificed on the 14th day postinjection for histological examinations. Mononuclear cell infiltration was detected around the ducts of salivary glands only in (B6 x bm12)F1 mice injected with B6 L3T4+ T cells. A moderate to marked level of cell infiltration was demonstrated in pancreas of (B6 x bm12)F1 recipients similar to nonobese diabetic (NOD) mice. By immunohistochemical examinations, infiltrating cells were shown to consist not only of L3T4+ but also of Lyt-2+ T cells, even after the inoculation of L3T4+ cells. These results are discussed in reference to mechanisms of organ-specific autoimmune diseases, especially insulitis in NOD mice which show insulin-dependent diabetes mellitus.