Prevention of lpr-graft-versus-host disease and transfer of autoimmune diseases in normal C57BL/6 mice by transplantation of bone marrow cells plus bones (stromal cells) from MRL/lpr mice.
C57BL/6 (B6) (H-2b) mice were lethally irradiated and then reconstituted with T cell-depleted MRL/Mp-lpr/lpr (MRL/lpr) (H-2k) bone marrow cells. The mice showed a short survival with splenic atrophy and fibrosis, as previously described as lpr-graft-vs-host disease (GVHD). However, when these mice received bone marrow transplantation (BMT) plus bone grafts (to recruit donor-derived stromal cells) from MRL/lpr mice, they survived for almost 1 yr without showing GVH symptoms, but showing autoimmune symptoms such as elevated serum IgG2a concentrations, autoantibody production and glomerulonephritis. When MRL/lpr bone marrow cells plus MRL/+ bones (instead of MRL/lpr bones) were transplanted into B6 mice, such improved survival was also obtained, although the MRL/+ bone grafts were less effective in prolonging survival than MRL/lpr bone grafts. H-2 typing of stromal cells in the bone marrow of the B6 mice revealed that the stromal cells had been replaced by donor(H-2k) derived stromal cells. Analyses of TCR repertoires showed that the percentage of CD4+V beta 8.1,2+ cells significantly decreased in the B6 mice that received bone marrow transplantation plus bone grafts from MRL/lpr mice. These findings suggest that stromal cells present in the bone marrow play a crucial role in the development of lpr-GVHD and autoimmune diseases.
Miyashima
S
S
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Nagata
N
N
Nakagawa
T
T
Hosaka
N
N
Takeuchi
K
K
Ogawa
R
R
Ikehara
S
S
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017154:Stromal Cells / Q000637:transplantation*; D013601:T-Lymphocytes / Q000276:immunology