Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation
Dissociation of hemopoietic chimerism and allograft tolerance after allogeneic bone marrow transplantation
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DOI：
10.4049/jimmunol.167.6.3043
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发表时间：
2001-09-15
影响因子：
4.4
通讯作者：
Maki, T
中科院分区：
文献类型：
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作者：
Umemura, A;Morita, H;Maki, T
稳定的造血嵌合体的产生被认为是骨髓移植（BMT）后同种异体移植耐受的先决条件。在这项研究中，我们证明，同种异体BMT与骨髓细胞（BMC）从任何敲除小鼠缺乏在CD4和CD8 T细胞或CD3E转基因小鼠缺乏T细胞和NK细胞保持高度的嵌合体，但未能诱导耐受供体特异性野生型皮肤移植。当用T细胞缺陷型BMC重建的小鼠的淋巴细胞被注射到辐射供体品系小鼠中时，它们增殖，而用野生型BMC重建的小鼠的淋巴细胞对供体同种异体抗原无反应。当供体型T细胞过继转移到给予T细胞缺陷型BMC的受体小鼠时，供体特异性同种异体移植耐受得以恢复。这些结果表明，供体T细胞植入是诱导同种异体移植耐受所必需的，但不是在异基因BMT后产生连续的造血嵌合体，并且高度的嵌合体不一定与特异性同种异体移植耐受相关。
Creation of stable hemopoietic chimerism has been considered to be a prerequisite for allograft tolerance after bone marrow transplantation (BMT). In this study, we demonstrated that allogeneic BMT with bone marrow cells (BMC) prepared from either knockout mice deficient in both CD4 and CD8 T cells or CD3E-transgenic mice lacking both T cells and NK cells maintained a high degree of chimerism, but failed to induce tolerance to donor-specific wild-type skin grafts. Lymphocytes from mice reconstituted with T cell-deficient BMC proliferated when they were injected into irradiated donor strain mice, whereas lymphocytes from mice reconstituted with wild-type BMC were unresponsive to donor alloantigens. Donor-specific allograft tolerance was restored when donor-type T cells were adoptively transferred to recipient mice given T cell-deficient BMC. These results show that donor T cell engraftment is required for induction of allograft tolerance, but not for creation of continuous hemopoietic chimerism after allogeneic BMT, and that a high degree of chimerism is not necessarily associated with specific allograft tolerance.