of sLE* This is the first report describing the experimental induction of a full-blown clinical syndrome strongly resembling systemic lupus erythematosus (SLE). The method used was the induction of a chronic graft-vs. -host reaction (GVHR) employing genetically nonautoimmune strains of mice. Many of the F1 mice undergoing a GVHR (GVH F1 mice) revealed the following pathological alterations: splenomegaly, periarteritis, immunecomplex glomerulonephritis accompanied by elevated proteinuria and ascites, dysgammaglobulinemia, persistently increased production of IgG in the spleen, and formation of autoantibodies to thymocytes, erythrocytes, nuclear antigens, double-stranded DNA, and antibodies deposited along the basement membrane of skin. In spite of the excessive T cell help, the GVH F1 animals failed to produce spontaneous serum antibodies to dextran and the bacteriophage fd. They also had no increased numbers of spontaneous indirect plaque-forming cells to sheep red blood cells and trinitrophenyl. These negative findings indicate that antigen has to be present during the GVHR to trigger antibody formation. This in turn suggests that the persistent presence of self-antigens was essential for the formation of IgG autoantibodies in GVH F1 mice. However, whereas autoantibodies typical of SLE were readily produced, none of the GVH F1 mice had autoantibodies to thyroglobulin, or other autoantibodies not typical of SLE. Conceivably, not only the presence of self-antigens, but also their antigenic configuration, may determine whether or not autoreactive B cells are successfully triggered during abnormal T-B cell cooperation. Given the lack of carrier-specific T helper cells in abnormal T-B cell cooperation, protein self-antigens, such as thyroglobulin, may be intrinsically less apt than the self-antigens involved in SLE to bind to the corresponding autoreactive B cells. The self-antigens involved in SLE, such as DNA and cell-surface epitopes, are assumed to be capable of multipoint high-avidity binding to and cross-linking of the Ig receptors of these B cells, thus providing an effective signal 1.

When comparing, in a murine model, the kind of graft-versus-host (GVH) disease (GVHD) induced by the donor strain DBA/2 on the one hand and several H-2-congenic resistant B10 donor strains on the other, we found that strain DBA/2 was a universal nonkilling GVH donor for H-2-incompatible nonirradiated F1 hybrid recipients. In this respect, DBA/2 T cells differed from those of the H-2-identical donor strain B10.D2 as well as those of other b10 donor strains. The inability of strain DBA/2 to kill by GVH reaction was not limited to certain H-2 incompatibilities in the F1 recipients, but was nonspecific. The inability to kill is determined by a dominant locus not linked to H-2. DBA/2 T cells were also incapable of inducing the severe suppression of hematocrit values, bone marrow erythropoiesis, thymic cell proliferation, and splenic IgG production in the F1 recipients that was observed after the injection of T cell from the B10 strains. However, DBA/2 T cells, in contrast with those of the B10 donor strains, were vigorous stimulators of IgG production in H-2-incompatible F1 hybrid recipients. Surprisingly, strain DBA/2 as well as the B10 donor strains had good capacity to generate anti-F1 TK cells. Taken together, these findings raise the possibility that lethal GVHD disease is not caused, or not caused exclusively, by donor killer T cells, but by those donor T cells that directly or indirectly induce a suppression of cell proliferation in certain vital organs of the recipient.

The immunochemical characteristics of granulocyte allo- and autoantibodies can easily be studied with indirect immunofluorescence techniques. The correlation of these properties with the serological behavior of the antibodies and the clinical condition in which they were found was studied. The investigations included the determination of immunoglobulin class, subclass, light-chain composition, as well as optimal temperature of activity. Complement fixation in vitro was also investigated. Striking differences were found between IgG and IgM antibodies in their serological properties, especially in the granulocytotoxicity and leukoagglutination tests at different temperatures. Differences in light-chain and IgG subclass compositions of the antibodies did not seem to play a role. In studying the distribution of granulocyte-specific antigens on normal granulocytes and granulocytes in all stages of development, it was found that, while NA1, NA2 and ND1 are present in the same quantity on the cells of an individual, the NB1 antigen is unequally distributed, both over ripe granulocytes and granulocyte precursors.