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)
Hosaka
N
N
First Department of Pathology, Kansai Medical University, Osaka, Japan.
Nagata
N
N
Nakagawa
T
T
Miyashima
S
S
Yasumizu
R
R
Ikehara
S
S
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018800:Thy-1 Antigens / Q000276:immunology; D014916:Whole-Body Irradiation
D018800:Thy-1 Antigens