Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions:: in vivo implications in transplanted patients
Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions:: in vivo implications in transplanted patients
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DOI：
10.1002/eji.200324266
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Rouas-Freiss, N
中科院分区：
文献类型：
--
作者：
Le Rond, S;Le Maoult, J;Rouas-Freiss, N
HL A-G通过抑制NK和CTL介导的细胞溶解和CD4(+)T细胞的同种异体增殖，对参与移植物排斥反应的主要效应细胞表现出免疫耐受特性。HL A-G在健康组织中的表达仅限于滋养层和胸腺，但在病理条件下可扩展到各种组织。在移植患者的同种异体移植活检和血清中检测到了HL A-G，这些患者表现出较好的移植物接受性。然而，参与这种从头表达HLA-G的细胞仍有待鉴定。通过流式细胞仪和共聚焦显微镜观察，我们发现在体外同种异体刺激后，CD4(+)和CD8(+)T细胞亚群均能表达膜结合的人类白细胞抗原-G1和/或可溶性的人类白细胞抗原-G5分子。这种HLA-G1/-G5的表达是在转录水平上调节的。利用针对人类白细胞抗原-G5内含子4保留序列的新型单抗5A6G7可以检测到可溶性的人类白细胞抗原-G5。最后，通过对移植患者的分析，提供了这些数据的生物学相关性，在这些患者中，我们发现了表达HLA-G的CD4(+)和CD8(+)T细胞。我们在此描述的人类白细胞抗原G阳性T细胞可能构成同种异体移植后人类白细胞抗原G的细胞来源，并可能参与改善移植受者对人类白细胞抗原G阳性移植患者的接受性。
HLA-G displays immunotolerogenic properties towards the main effector cells involved in graft rejection through inhibition of NK- and CTL-mediated cytolysis and CD4(+)T cell alloproliferation. HLA-G expression is restricted in healthy tissues to trophoblast and thymus but is extended to various tissues under pathological conditions. HLA-G was detected in allograft biopsies and sera from transplanted patients who displayed a better graft acceptance. However, the cells involved in such de novo expression of HLA-G remain to be characterized. By flow cytometry and confocal microscopy, we demonstrated that, following allogeneic stimulation in vitro, both CD4(+) and CD8(+) T cell subsets can express membrane-bound HLA-G1 and/or soluble HLA-G5 molecules. Such HLA-G1/-G5 expression is regulated at the transcriptional level. Soluble HLA-G5 could be detected by using a novel monoclonal antibody, 5A6G7, specific for the intron 4-retaining sequence of HLA-G5. Finally, the biological relevance of these data was provided by analysis of transplanted patients in whom we identified both CD4(+) and CD8(+) T cells expressing HLA-G. The HLA-G-positive T cells we describe here may constitute a cellular source of HLA-G after allotransplantation and may be involved in the improved graft acceptance which is observed in HLA-G-positive transplanted patients.