CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
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DOI：
10.1111/ajt.13613
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Kirk AD
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文献类型：
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作者：
Espinosa J;Herr F;Tharp G;Bosinger S;Song M;Farris AB 3rd;George R;Cheeseman J;Stempora L;Townsend R;Durrbach A;Kirk AD
贝拉西普是一种B7特异性融合蛋白，用于通过阻断T细胞共刺激来预防同种异体移植排斥反应。通常有效，但在相当一部分患者中不能预防急性排斥反应。在实验模型中，记忆T细胞介导共刺激阻断抵抗性排斥（CoBRR），但这在人类中仍然不确定。为了探索个体免疫细胞表型与CoBRR之间的关系，我们研究了接受贝拉西普或常规钙调磷酸酶免疫抑制的患者。我们确定了移植前存在的CD 57 + PD 1 − CD 4 T细胞群与CoBRR相关。与认识到CD 57是CD 8 T细胞上衰老标志物的数据相反，我们发现了与CD 4 T细胞上的CD 57相关的非衰老细胞溶解表型。此外，CD 57 + CD 4 T细胞：表达高水平的与实验性CoBRR有关的粘附分子; CD 28呈阴性;表达广泛定义同种异体移植排斥反应的转录表型;并且被证明存在于排斥的人肾同种异体移植物中。这些数据表明临床CoBRR中存在CD 57 + CD 4 T细胞，如果前瞻性验证，该特征可以识别基于贝拉西普治疗的急性排斥反应风险较高的患者。
Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate costimulation blockade-resistant rejection (CoBRR), but this remains undefined in humans. To explore relationships between individuals’ immune cell phenotypes and CoBRR, we studied patients receiving belatacept or conventional calcineurin inhibitor-based immunosuppression. We identified a population of CD57+PD1− CD4 T cells present prior to transplantation that correlated with CoBRR. Contrary to data recognizing CD57 as a marker of senescence on CD8 T cells, we discovered a non-senescent, cytolytic phenotype associated with CD57 on CD4 T cells. Moreover, CD57+ CD4 T cells: expressed high levels of adhesion molecules implicated in experimental CoBRR; were CD28 negative; expressed a transcriptional phenotype broadly defining allograft rejection; and were shown to be present in rejecting human kidney allografts. These data implicate CD57+ CD4 T cells in clinical CoBRR and if prospectively validated, this characteristic could identify patients at higher risk for acute rejection on belatacept-based therapy.