Attempts at standardization of lupus-like graft-vs-host disease: inadvertent repopulation by DBA/2 spleen cells of H-2-different nonirradiated F1 mice.
By induction of a suitable graft-vs-host reaction (GVHR) in nonirradiated, H-2-incompatible F1 mice, one can induce a syndrome strongly resembling systemic lupus erythematosus (SLE). The aim of the present study was to standardize the kind and number of DBA/2 donor cells required for optimal induction of this SLE-like GVH disease (GVHD). Groups of adult (C57BL/10 x DBA/2)F1 (BDF1) mice were injected i.v. with increasing numbers of DBA/2 spleen and lymph-node cells. We found that doses of 100 x 10(6) to 180 x 10(6) spleen and lymph-node cells provided a suitable donor-cell inoculum, whereas doses of donor cells below 100 x 10(6) were suboptimal and doses higher than 180 x 10(6) cells were supraoptimal for the induction of SLE-like GVHD. In a number of those F1 recipients that had received the donor-cell inocula composed of spleen cells, the duration of autoantibody formation was surprisingly brief. This appeared to be due to the fact that these GVH F1 mice were rapidly repopulated by lympho-hemopoietic donor cells. Even after the highest doses of DBA/2 spleen and lymph-node cells administered, this repopulation was not preceded by symptoms of acute GVH disease. Repopulation was avoided and a severe SLE-like disease induced when a mixture deficient in hemopoietic cells, i.e., 280 x 10(6) DBA/2 lymph-node and thymus cells, was used as donor-cell inoculum. Taken together, we reached three conclusions. First, the induction of full-blown SLE-like GVHD depends not only on the injection of a sufficient number of donor T cells but also on the continuous presence of F1 lymphoid cells, which seem to serve as stimulator cells. Second, in addition to the lymphoid hyperplasia and immune-complex glomerulonephritis (ICGN) described previously, the GVHR-induced lesions presenting themselves in the context of SLE-like autoimmunity include a Sjögren-like lymphoid infiltration of the salivary gland, a ubiquitous periarteritis, and a lymphoid infiltration of the bile ducts that is reminiscent of primary biliary cirrhosis. Third, the repopulation by donor cells of nonirradiated, H-2-incompatible hosts need not be accompanied by GVH mortality or symptoms of acute GVHD.
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006087:Graft vs Host Reaction; D006183:H-2 Antigens / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011507:Proteinuria / Q000175:diagnosis; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D013950:Thymus Gland / Q000473:pathology
D001323:Autoantibodies; D006183:H-2 Antigens; D004247:DNA