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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1862-1868
Treatment of intractable autoimmune diseases in MRL/lpr mice
using a new strategy for allogeneic bone marrow transplantation
Taketoshi Kushida,
Muneo Inaba,
Kenji Takeuchi,
Kikuya Sugiura,
Ryokei Ogawa, and
Susumu Ikehara
From the First Department of Pathology, and Department
of Orthopedic Surgery, Kansai Medical University, Moriguchi City,
Osaka, Japan.
A new bone marrow transplantation (BMT) method for treating severe
autoimmune diseases in chimeric resistant MRL/lpr mice is presented.
The method consists of fractionated irradiation (5.5 Gy × 2),
followed by portal venous (PV) injection of whole bone marrow cells
(BMCs) from allogeneic normal C57BL/6 (B6) mice and intravenous (IV)
injection of whole B6 BMCs 5 days after the PV injection (abbreviated
as 5.5 Gy × 2 + PV + IV). All recipients survived more than
1 year after this treatment (more than 64 weeks after birth). Abnormal
T cells
(Thy1.2+/B220+/CD3+/CD4 /CD8)
present in MRL/lpr mice before the treatment disappear, and hematolymphoid cells are reconstituted with donor-derived cells. The
treated mice are free from autoimmune diseases. Levels of autoantibodies (IgG/IgM anti-ssDNA antibodies and IgG/IgM rheumatoid factors) decrease to normal levels. Successful cooperation is achieved
among T cells, B cells, and antigen-presenting cells (APCs) of the
treated MRL/lpr mice when evaluated by in vitro anti-SRBC responses.
Newly developed T cells are tolerant to both donor (B6)-type and host
(MRL/lpr)-type major histocompatibility complex (MHC) determinants.
These findings clearly indicate that severe autoimmune diseases in
MRL/lpr mice are completely ameliorated by the treatment without
recourse to immunosuppressants, and that the treated MRL/lpr mice show
normal immune functions, strongly suggesting that this strategy would
be applicable to humans.
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