Journal
BLOOD
Volume 109, Issue 3, Pages 1307-1315Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-05-022772
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Funding
- NHLBI NIH HHS [R01 HL063452, R01 HL63452] Funding Source: Medline
- NIAID NIH HHS [P01 AI056299] Funding Source: Medline
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Multiply-transfused individuals are at higher risk for BM rejection. We show that whereas allosensitization resulted in the priming of both cellular and humoral immunity, preformed antibody was the major barrier to engraftment. The generation of cross-reactive alloantibody led to rejection of BM of a different MHC-disparate strain. Imaging studies indicated that antibody-mediated rejection was very rapid (< 3 hours) in primed recipients, while T-cell-mediated rejection in nonprimed mice took more than 6 days. Antibody-mediated BM rejection was not due to a defect in BM homing as rejection occurred despite direct intra-BM infusion of donor BM. Rejection was dependent upon host FcR(+) cells. BM cells incubated with serum from primed mice were eliminated in nonprimed recipients, indicating that persistent exposure to high-titer antibody was not essential for rejection. High donor engraftment was achieved in a proportion of primed mice by mega-BM cell dose, in vivo T-cell depletion, and high-dose immunoglobulin infusion. The addition of splenectomy to this protocol only modestly added to the efficacy of this combination strategy. These data demonstrate both rapid alloantibody-mediated elimination of BM by host FcR(+) cells and priming of host anticionor T cells and suggest a practical strategy to overcome engraftment barriers in primed individuals.
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