Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+ CD25+ T-cell-dependent mechanism.
Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+ CD25+ T-cell-dependent mechanism.
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DOI：
10.1182/blood-2005-07-3045
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发表时间：
2005-11
期刊：
影响因子：
20.3
通讯作者：
K. Matsuoka;T. Ichinohe;D. Hashimoto;S. Asakura;M. Tanimoto;T. Teshima
中科院分区：
文献类型：
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作者：
K. Matsuoka;T. Ichinohe;D. Hashimoto;S. Asakura;M. Tanimoto;T. Teshima
供体可用性的缺乏是广泛使用异基因造血干细胞移植的主要限制，因此鉴定较少免疫原性HLA错配将是有益的。在妊娠期间通过双向经胎盘传递的母体和胎儿抗原可诱导后代对非遗传性母体抗原（NIMAs）和母体对遗传性父系抗原（IPAs）的耐受。使用小鼠骨髓移植（BMT）模型，我们发现，从NIMA暴露供体的“儿童到母亲”BMT以抗原特异性方式降低了移植物抗宿主病的发病率和死亡率;然而，从IPA暴露供体的“母亲到儿童”BMT没有。NIMA互补骨髓移植保留了移植物抗白血病的作用，有利于免疫重建，从而导致骨髓移植后的结果显着改善。这些致耐受性NIMA效应通过供体接种物中的CD 4 + CD 25+细胞的消耗而完全消除，从而表明CD 4 + CD 25+调节性T细胞参与致耐受性NIMA效应。因此，我们的研究结果可能对临床BMT的性能产生深远的影响，同时也可能有助于开发新的策略，在没有HLA相同供体的情况下使用NIMA不匹配的供体。
The lack of donor availability is a major limitation to the widespread use of allogeneic hematopoietic stem cell transplantation, and therefore it would be beneficial to identify less immunogenic HLA mismatches. The maternal and fetal antigens that are transmitted through the bidirectional transplacental passage during pregnancy may induce tolerance to noninherited maternal antigens (NIMAs) in offspring and to inherited paternal antigens (IPAs) in the mother. Using mouse models of bone marrow transplantation (BMT), we found that a "child-to-mother" BMT from a NIMA-exposed donor reduced the morbidity and mortality of graft-versus-host disease in an antigen-specific manner; however, a "mother-to-child" BMT from an IPA-exposed donor did not. The NIMA-complementary BMT preserved the graft-versus-leukemia effects and favored the immune reconstitution, thus resulting in a marked improvement of the outcome after BMT. These tolerogenic NIMA effects were completely abolished by the depletion of CD4+ CD25+ cells from the donor inocula, thus suggesting the involvement of CD4+ CD25+ regulatory T cells in the tolerogenic NIMA effects. Our findings may therefore have profound implications on the performance of clinical BMT while also potentially helping to develop new strategies for using a NIMA-mismatched donor in the absence of an HLA-identical donor.