TY - JOUR
T1 - Rapamycin and T cell costimulatory blockade as post-transplant treatment promote fully MHC-mismatched allogeneic bone marrow engraftment under irradiation-free conditioning therapy
AU - Wu, T.
AU - Sozen, H.
AU - Luo, B.
AU - Heuss, N.
AU - Kalscheuer, H.
AU - Lan, P.
AU - Sutherland, D. E.R.
AU - Hering, B. J.
AU - Guo, Z.
N1 - Funding Information:
This work was partly supported by grants awarded by the Juvenile Diabetes Foundation International and by the American Diabetes Association.
PY - 2002
Y1 - 2002
N2 - Hematopoietic macrochimerism, established by bone marrow transplantation, can be used as an approach for treating autoimmune disease and inducing transplant tolerance. In this study, we investigated whether a stable, high level of fully MHC-mismatched hematopoietic macrochimerism can be induced by using irradiation-free protocols, and whether rapamycin and T cell costimulatory blockades (anti-CD40L monoclonal antibody (mAb) and CTLA4Ig) as post-transplant treatment promote bone marrow engraftment. Donorspecific blood transfusion (DST), anti-lymphocyte serum (ALS), busulfan, and cyclophosphamide were given pretransplantation. Balb/c (H-2d) bone marrow cells, at a dose of 4 x 107, were infused into each C57BL/6 mouse (H-2b). Rapamycin, anti-CD40L mAb, and CTLX4Ig were then administered, either alone or in combination. Without ALS or busulfan and cyclophosphamide, macrochimerism can only rarely be induced. Donor-specific transfusion (DST) enhances induction of hematopoietic macrochimerism. Rapamycin, anti-CD40L mAb and CTLA4Ig, alone or in combination, induce a stable and high level of hematopoietic macrochimerism. In the chimeric mice, donor-derived cells were detected in all lymphohematopoietic tissues and donor-specific tolerance was induced in vitro. We conclude that a stable and high level of fully MHC-mismatched hematopoietic macrochimerism can be induced in mice after transplanting a single modest dose of bone marrow cells without irradiation. Rapamycin and T cell costimulatory blockade as post-transplant treatment promote bone marrow engraftment.
AB - Hematopoietic macrochimerism, established by bone marrow transplantation, can be used as an approach for treating autoimmune disease and inducing transplant tolerance. In this study, we investigated whether a stable, high level of fully MHC-mismatched hematopoietic macrochimerism can be induced by using irradiation-free protocols, and whether rapamycin and T cell costimulatory blockades (anti-CD40L monoclonal antibody (mAb) and CTLA4Ig) as post-transplant treatment promote bone marrow engraftment. Donorspecific blood transfusion (DST), anti-lymphocyte serum (ALS), busulfan, and cyclophosphamide were given pretransplantation. Balb/c (H-2d) bone marrow cells, at a dose of 4 x 107, were infused into each C57BL/6 mouse (H-2b). Rapamycin, anti-CD40L mAb, and CTLX4Ig were then administered, either alone or in combination. Without ALS or busulfan and cyclophosphamide, macrochimerism can only rarely be induced. Donor-specific transfusion (DST) enhances induction of hematopoietic macrochimerism. Rapamycin, anti-CD40L mAb and CTLA4Ig, alone or in combination, induce a stable and high level of hematopoietic macrochimerism. In the chimeric mice, donor-derived cells were detected in all lymphohematopoietic tissues and donor-specific tolerance was induced in vitro. We conclude that a stable and high level of fully MHC-mismatched hematopoietic macrochimerism can be induced in mice after transplanting a single modest dose of bone marrow cells without irradiation. Rapamycin and T cell costimulatory blockade as post-transplant treatment promote bone marrow engraftment.
KW - Bone marrow transplantation
KW - Chimerism
KW - Immunosuppression
KW - Mice
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U2 - 10.1038/sj.bmt.1703574
DO - 10.1038/sj.bmt.1703574
M3 - Article
C2 - 12098061
AN - SCOPUS:0036327705
SN - 0268-3369
VL - 29
SP - 949
EP - 956
JO - Bone marrow transplantation
JF - Bone marrow transplantation
IS - 12
ER -