Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28- T cells

Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28- T cells
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DOI:
10.1093/intimm/10.6.775
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发表时间:
1998-06-01
影响因子:
4.4
通讯作者:
Suciu-Foca, N
Suciu-Foca, N
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Z;Tugulea, S;Suciu-Foca, N

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被引文献

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特异性抑制宿主对供体HLA抗原的免疫反应仍然是临床移植的最终目标。然而,尽管付出了相当大的努力,异体特异性人类抑制性T细胞(T-s)一直难以产生。在这里,我们发现同种特异性和异种特异性T-s可以通过在混合淋巴细胞培养中多次启动人T细胞来提高。T-s来自CD8(+)CD28(-)亚群,并特异性识别用于体外免疫的抗原呈递细胞(APC)表达的MHC I类抗原。异体T-s阻止靶APC上B7分子的上调,干扰T辅助细胞(T-h)激活所需的CD28-B7相互作用。这些发现为特异性免疫抑制疗法的发展提供了基础。
Specific suppression of the host's immune response to donor HLA antigens remains the ultimate goal for clinical transplantation. In spite of considerable effort, however, allospecific human suppressor T cells (T-s) have been difficult to generate. Here we show that allospecific and xenospecific T-s can be raised by multiple priming of human T cells in mixed lymphocyte cultures. T-s derive from the CD8(+)CD28(-) subset and recognize specifically the MHC class I antigens expressed by antigen-presenting cells (APC) used for in vitro immunization. Allospecific T-s prevent the up-regulation of B7 molecules on target APC, interfering with the CD28-B7 interaction required for T helper (T-h) activation. These findings provide a basis for the development of specific immunosuppressive therapy.