Analyses of lpr-GVHD by adoptive transfer experiments using MRL/lpr-Thy-1.1 congenic mice

When MRL/Mp- +/+ (MRL/+) mice are lethally irradiated and then reconstituted with MRL/Mp-lpr/lpr (MRL/lpr) spleen and/or bone marrow cells (BMCs), the mice develop a graft-versus-host disease (GVHD)-like syndrome which is known as lpr-GVHD. We analyzed lpr-GVHD by adoptive transfer experiments using congenic MRL/lpr-Thy-1.1 mice to distinguish the donor and recipient cells. MRL/+ mice were lethally (9.5 Gy) irradiated and then reconstituted with BMCs of MRL/lpr-Thy-1.1 mice treated with anti-Thy-1.1 monoclonal antibody (mAb) plus complement (C). The mice were sacrificed 5 to 6 weeks after bone marrow transplantation (BMT), and the spleen cells were transferred to second recipients. The second recipients (MRL/+ or MRL/lpr mice) were non-irradiated, sublethally (6 Gy) irradiated or lethally (9.5 Gy) irradiated. The lethally irradiated mice were also injected with syngeneic BMCs treated with anti-Thy-1.2 mAb plus C. When whole spleen cells (1 x 10(8) were injected into lethally irradiated MRL/+ mice, the mice showed short survival (1.2-1.5 months) and severe histological changes in the spleen (atrophy and fibrosis), liver (lymphoid infiltration in the Glisson's sheath) and lung (lymphoid infiltration around the bronchus and vessel). The sublethally irradiated MRL/+ mice at 2 months after transfer showed histological changes similar to the lethally irradiated MRL/+ recipients, although the former survived more than 3 months, suggesting that histological changes do not reflect on mortality. These GVH-like diseases were not transferable to MRL/lpr mice; they developed autoimmune diseases.(ABSTRACT TRUNCATED AT 250 WORDS)