Analyses of lpr-gvhd by adoptive transfer experiments using mrl/lpr-thy-1.1 congenic mice
作者:
HosakaNaoki,
NagataNorikazu,
NakagawaTakuma,
MiyashimaShigeo,
YasumizuRyoji,
IkeharaSusumu,
期刊:
Autoimmunity
(Taylor Available online 1994)
卷期:
Volume 17,
issue 3
页码: 217-224
ISSN:0891-6934
年代: 1994
DOI:10.3109/08916939409010657
出版商: Taylor&Francis
关键词: MRL/lpr mice;MRL/+ mice;lpr-GVHD;adoptive transfer;T cell subsets
数据来源: Taylor
摘要:
When MRL/Mp - + / + (MRU +) 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 (1×108) 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. The percentage of donor CD4+cells in the lethally irradiated MRL/lpr mice was similar to that in the lethally irradiated MRL/ + mice, but CD8+cell numbers were substantially less. The effector cells were characterized using lethally irradiated MRL/+ mice as second recipients. The injection of T cell-enriched (nylon wool-nonadherent) effector cells induced shorter survival and more severe splenic atrophy. In contrast, the injection of effector cells treated with anti-Thy-1.1 mAb plus C induced longer survival, indicating that T cells are effector cells. The injection of CDS+cells induced shorter survival than that of CD4+cells. The injection of a mixture of CD4+and CD8+cells showed similar survival to that of CD8+cells alone. The histological grades of spleens strongly correlated with the percentage of donor CD4+cells, but only loosely with the percentage of donor CD8+cells. These findings suggest that CD8+T cells are responsible for mortality, while CD4+T cells induce splenic atrophy and fibrosis in the development of lpr-GVHD. We also discuss these findings in relation to possible mechanisms of lpr-GVHD.
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