Diseases caused by reactions of T lymphocytes to incompatible structures of the major histocompatibility complex. VII. Immune-complex glomerulonephritis.

A chronic graft-vs-host reaction (GVHR) was induced in nonirradiated (C57BL/10 × DBA/2) F1 mice by the injection of lymphoid cells from DBA/2 donors. This led to the development of immune-complex glomerulonephritis (ICGN) in the F1 mice undergoing GVHR (GVH F, mice). Our results demonstrate that the ICGN in GVH F1 mice is an immune-complex disease that is triggered by an alloimmune reaction of parental strain T lymphocytes toward the H-2-incompatible structures of the F1 recipients, which results in abnormal T-B cell cooperation. For ICGN to be induced, the presence of the F1 hybrid's own T lymphocytes was not required; in contrast, the absence of F1 T cells (B F1 mice) greatly facilitated the induction of ICGN by donor T cells. This finding indicated that autologous T cells of the F1 recipient suppress the induction of ICGN by the GVHR. Host-derived antibodies were evidently involved in the pathogenesis of GVHR-induced ICGN, because antibodies carrying the host-derived lg-1b allotype were detected along the glomerular basement membrane (GBM) of the GVH F1 mice. This observation conformed with the finding that almost all the cells in the spleens of glomerulonephritic GVH F1 mice were of host origin. Significant amounts of antibody with specificity for nuclear antigens and murine leukemia virus (MuLV) could be eluted from the kidneys with ICGN. ICGN in this model is part of a systemic lupus erythematosus- (SLE) like syndrome. Our results indicate that as far as the nature of the immune-complex deposits is concerned, there is a final common pathway to ICGN in both human SLE and different mouse models of SLE, in that the glomerular immune complexes involve autoantibodies to nuclear antigens and antiviral antibodies.