Donor-specific transplantation tolerance:: The paradoxical behavior of CD4+CD25+ T cells
Donor-specific transplantation tolerance:: The paradoxical behavior of CD4+CD25+ T cells
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DOI：
10.1073/pnas.0400084101
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发表时间：
2004-07-06
影响因子：
11.1
通讯作者：
Waldmann, H
中科院分区：
文献类型：
--
作者：
Graca, L;Le Moine, A;Waldmann, H
为了研究调节性T细胞能够预防移植排斥反应的抗原特异性，我们开发了两种不同的策略来实现对完全不相合的皮肤移植的耐受性。针对CD_4、CD_8和CD_(154)(CD40配体)的非耗竭抗体组合可诱导对完全不相合的同种异体皮肤移植的显性移植耐受。这种耐受性是抗原特异性的，由调节性T细胞介导，并可以通过对幼稚淋巴细胞的连锁抑制来扩展。同样的方案，当与异基因骨髓结合时，能够发展出混合的造血嵌合体和缺失耐受。虽然我们不能排除一些调节性T细胞可能在嵌合体小鼠中持续存在，但这些细胞不足以调节连锁抑制。无论是来自幼鼠还是从耐受小鼠身上获得的CD4(+)CD25(+)T细胞，总是能够阻止幼稚的CD4(+)T细胞对皮肤移植物的排斥反应，而且对耐受性供体抗原没有明显的特异性。这些数据质疑是否仅有CD4(+)CD25(+)调节性T细胞能够解释显性移植耐受的抗原特异性。
To investigate the antigen specificity of regulatory T cells capable of preventing transplant rejection, we have developed two different strategies to achieve tolerance to fully mismatched skin grafts in euthymic mice. A combination of nondepleting Abs targeting CD4, CD8, and CD154 (CD40 ligand) induces dominant transplantation tolerance to fully mismatched skin allografts. Such tolerance is antigen-specific, mediated by regulatory T cells, and can be extended through linked suppression to naive lymphocytes. The same protocol, when combined with allogeneic bone marrow, enables the development of mixed hematopoietic chimerism and deletional tolerance. Although we cannot exclude that some regulatory T cells may persist in chimeric mice, these cells are insufficient to mediate linked suppression. CD4(+)CD25(+) T cells, whether taken from naive mice or from mice tolerized through either treatment protocol, were always able to prevent rejection of skin grafts by naive CD4(+) T cells, and did so with no demonstrable specificity for the tolerizing donor antigens. Such data question whether CD4(+)CD25(+) regulatory T cells alone can account for the antigen specificity of dominant transplantation tolerance.