Immune tolerance to combined organ and bone marrow transplants after fractionated lymphoid irradiation involves regulatory NK T cells and clonal deletion
Immune tolerance to combined organ and bone marrow transplants after fractionated lymphoid irradiation involves regulatory NK T cells and clonal deletion
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DOI：
10.4049/jimmunol.169.10.5564
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发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Strober, S
中科院分区：
文献类型：
--
作者：
Higuchi, M;Zeng, DF;Strober, S
据报道，在实验动物和人类中，对器官移植的免疫耐受是在宿主进行非清髓性调节和输注供体骨髓细胞后发生的。我们研究了小鼠心脏移植免疫耐受的机制，在MHC不相合的宿主中，移植后通过多剂量淋巴组织照射、耗竭性抗T细胞抗体和输注供者骨髓细胞进行2周疗程的条件处理后出现混合嵌合体。当使用NK T细胞显著减少的CD1(-/-)或J(α)281(-/-)宿主代替野生型宿主时，尽管出现了混合嵌合体，但预适应方案未能诱导对同种异体心脏移植的耐受。通过从含有CD1反应性T细胞的野生型小鼠的骨髓中输注浓缩的T细胞，可以恢复CD1(-/-)宿主的耐受性，但不能从CD1(-/-)主体型小鼠那里输注。给予该方案的IL-4(-/-)和IL-10(-/-)宿主均不能诱导耐受，尽管在IL-10(-/-)宿主中发生了嵌合体和供体MHC-AGS的克隆性缺失。我们的结论是，对骨髓移植的免疫耐受涉及克隆性缺失，而在该模型中，对心脏移植的耐受也涉及调节性CD1反应性NK T细胞。
Immune tolerance to organ transplants has been reported in laboratory animals and in humans after nonmyeloablative conditioning of the host and infusion of donor bone marrow cells. We examined the mechanisms of immune tolerance to mouse cardiac allografts in MHC-mismatched hosts that developed mixed chimerism after posttransplant conditioning with a 2-wk course of multiple doses of lymphoid tissue irradiation, depletive anti-T cell Abs, and an infusion of donor bone marrow cells. When CD1(-/-) or J(alpha)281(-/-) hosts with markedly reduced NK T cells were used instead of wild-type hosts, then the conditioning regimen failed to induce tolerance to the heart allografts despite the development of mixed chimerism. Tolerance could be restored to the CD1(-/-) hosts by infusing enriched T cells from the bone marrow of wild-type mice containing CD1-reactive T cells but not from CD1(-/-) host-type mice. Tolerance could not be induced in either IL-4(-/-) or IL-10(-/-) hosts given the regimen despite the development of chimerism and clonal deletion of host T cells to donor MHC-Ags in the IL-10(-/-) hosts. We conclude that immune tolerance to bone marrow transplants involves clonal deletion, and tolerance to heart allografts in this model also involves regulatory CD1-reactive NK T cells.