[Analysis of the mechanism of graft-vs-host like disease in [lpr/lpr----+/+] chimera].
It was recently demonstrated that MRL-lpr lymphoid cells transferred into lethally irradiated MRL- +mice unexpectedly failed to induce the early onset of lupus syndrome and massive lymphadenopathy of the donor, instead they caused a severe wasting syndrome resembling graft-vs-host (GvH) disease. The present studies were carried out to characterize the cellular events involved in the severe GvH-like reaction developed in C57BL/6 (B6) recipients of B6-lpr spleen cells, designated as [B6-lpr----B6] chimeras. [B6-lpr----B6] chimeras showed at 2 weeks post transplantation marked splenomegaly consisting predominantly of Lyt2+ T cells (approximately 70%), and subsequently developed acute and severe depletion in spleen cells causing spleen atrophy and fibrosis. Spleen cells from chimeras at 2 weeks posttransfer were not cytotoxic to both recipient and donor ConA blast target cells. In contrast, those cells (irradiated to 3000 rad) considerably suppressed ConA-induced proliferative responses of B6 spleen cells. These nonspecific suppressor cells expressed Thy1 and Lyt2 antigens, but lacked L3T4 and B220 antigens. Furthermore, elimination of Thy1+ or B220+ but neither L3T4+ nor Lyt2+ cells from B6-lpr spleen cells before transfer retarded the generation of nonspecific suppressor cells but did not abrogate the GvH-like disease. These results suggest that the GvH-like disease and lymphoid atrophy in [B6-lpr----B6] chimeras were mediated by Lyt2+ suppressor T cells, and that B220+ T cells played a crucial role in the induction of these suppressor cells. The cell transfer model reported here may be very useful in understanding the immunological function of B220+ T cells in vivo.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division; D002678:Chimera; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007518:Isoantibodies / Q000032:analysis; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000954:Antigens, Surface; D007518:Isoantibodies; C035678:anti-Thy antibody