Glomerulopathy induced by graft-versus-host reaction in the rat. Requirement of donor CD4+ T lymphocytes and MHC class II incompatibility at the lymphoid compartment

Graft-versus-host reactions (GVHR) can be associated with several autoimmune phenomena involving the kidney as a target organ. By transferring lymphocytes of AO rats into complete Freund's adjuvant-pretreated (AO x BN)F1 hybrids, a dose-dependent GVHR with glomerulopathy was experimentally induced. IgM, IgG1, and IgG2a were deposited in the mesangial area and along the glomerular basement membrane. Eluted immunoglobulins from diseased kidneys bound to normal basement membranes and especially to laminin. Anti-laminin reactivity was also present in sera from F1 recipients with GVHR. Parental CD4+ T lymphocytes were required and sufficient to induce GVHR and glomerulopathy in sublethally irradiated F1 hybrids. Using various F1 hybrids, MHC class II incompatibility was shown to be required for the induction of GVHR-associated glomerulopathy. Across MHC class I incompatibility, GVHR without glomerulopathy could be induced, provided that both CD4+ and CD8+ donor T lymphocytes were administered. Finally, MHC incompatibility between donor T lymphocytes and the recipient non-lymphoid compartment was found to be sufficient for the induction of GVHR, but not for GVHR-associated glomerulopathy. The results indicate that alloreactive donor CD4+ T lymphocytes have to interact directly with MHC class II alloantigen bearing host B lymphocytes in order to stimulate the latter to produce (auto-)antibodies. GVHR-induced glomerulopathy shares several immunopathological features with HgCl2-induced autoimmune glomerulopathy in the rat