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Blood, 15 January 2001, Vol. 97, No. 2, pp. 557-564
TRANSPLANTATION
Allogeneic chimerism with low-dose irradiation, antigen
presensitization, and costimulator blockade in H-2 mismatched
mice
Peter J. Quesenberry,
Suju Zhong,
Han Wang, and
Marc Stewart
From the Cancer Center, University of Massachusetts
Medical Center, Worcester, MA.
We have previously shown that the keys to high-level nontoxic
chimerism in syngeneic models are stem cell toxic, nonmyelotoxic host
treatment as provided by 100-cGy whole-body irradiation and relatively
high levels of marrow stem cells. This approach was unsuccessful in H-2
mismatched B6.SJL to BALB/c marrow transplants, but with tolerization,
stable multilineage chimerism was obtained. Ten million B6.SJL spleen
cells were infused intravenously into BALB/c hosts on day  10 and
(MR-1) anti-CD40 ligand monoclonal antibody (mAb) injected
intraperitoneally at varying levels on days 10, 7, 3, 0, and +3
and the BALB/c mice irradiated (100 cGy) and infused with 40 million
B6.SJL/H-2 mismatched marrow cells on day 0. Stable
multilineage chimerism at levels between 30% to 40% was achieved in
the great majority of mice at 1.6 mg anti-CD40 ligand mAb per injection
out to 64 weeks after transplantation, without graft-versus-host
disease. The transplanted mice were also tolerant of donor
B6.SJL, but not third-party CBA/J skin grafts at 8 to 9 and 39 to 43 weeks after marrow transplantation. These data provide a unique model
for obtaining stable partial chimerism in H-2 mismatched
mice, which can be applied to various clinical diseases of man
such as sickle cell anemia, thalassemia, and autoimmune disorders.
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