[Analysis of acute graft-vs-host like reaction in [B6-lpr----B6] spleen chimera mice]

The lpr autoimmune mice develop massive lymphadenopathy and autoimmune disease. Transfer of lpr autoimmune disease to normal mice by bone marrow transplantation did not succeed, but caused a severe wasting syndrome like graft-vs-host (GvH) disease (lpr-GvH). We previously demonstrated that the transfer of B6-lpr spleen cells to B6 mice ([B6-lpr----B6] chimera) caused acute GvH-like disease accompanied by remarkable CD8+ T cell expansion, and that chimera spleen cells had suppressive activity on mitogen responses of spleen cells from normal mice. In this paper, I studied strain difference of acute lpr-GvH disease and mechanism of suppressive activity further. [B6-lpr----B6] chimera spleen contained more than 70% of CD8+ cells. However, [MRL-lpr----MRL-(+)] chimera and [C3H-lpr----C3H] chimera contained less than 20% of CD8+ cells. Both B220+ DN T cells and CD 8+ T cells were requisite for expansion of CD8+ T cell in the chimera spleen. Mixed chimera experiments using CD8+ T cells from B6-lpr-Thy1.1 mice and B220+ DN T cells from B6-lpr mice showed that CD8+ but not B220+ DN T cells were direct precursors of expanding CD8+ T cells. The mechanism of suppressive activity on Con A responses was different from that on LPS responses. A cell-to-cell interaction was essential for suppression of Con A response without involvement of CD8- cells, while suppression of LPS responses was mainly exhibited by soluble factors. Suppression of LPS responses was abrogated by the presence of anti-IFN-gamma monoclonal antibody, suggesting that those factors contain IFN-gamma. These data suggest that CD8+ T cells from B6-lpr mice were activated by unidentified antigen(s) which were expressed by B6 but not B6-lpr cells, and that IFN-gamma and/or unknown inflammatory factors secreted by the CD8+ T cells induced pathological outcome indistinguishable from GvH reaction in B6 recipient mice.