成双成对未必好
本文由汉氏联合专家团队翻译
急性移植物抗宿主病是因为在造血干细胞移植过程中供者T细胞对异源肽---主要组织相容性复合体抗原的强烈反应。既往的研究并未发现保护性免疫或病理性同种异体反应有选择性的T细胞亚群。华盛顿大学医学院的研究人员发现在异基因HSCT后发生aGVHD患者一小部分外周血T细胞表面天然表达两种T细胞受体（TCR）。
来自aGVHD患者的双TCR --T细胞在体外有激活的表型，并产生致病性细胞因子。从一例发作期aGVHD患者得到双受体T细胞克隆对错配的受者人白细胞抗原（HLA）有特异性反应，揭示了同种异体反应性的病理学。人双TCR—T细胞被同种异体刺激原体外强烈激活和扩增，不成比例地激发识别主要HLA和次要HLA抗原的T细胞库，为观察到的双TCR—T细胞在aGVHD患者体内的活动提供了解释。这些结果证明双TCR-T细胞是分析调节GVHD的T细胞亚群重要靶点，并且是一个可能的预后指标。
引申：利用间充质干细胞的免疫调节功能可以预防aGVHD的发生和减轻症状，在美国已经进入到三期临床阶段。国内也开始间充质干细胞治疗GVHD的研究，例如汉氏联合生物技术有限公司和昂赛细胞基因工程有限公司都在开展MSC的治疗应用潜能开发。据初步的临床报告，间充质干细胞的治疗都取得很明显疗效，部分患者摆脱了大量使用药物的困扰。
原文摘选：
Acute graft-versus-host disease (aGVHD) results from a robust response of donor T cells transferred during hematopoietic stem cell transplantation (HSCT) to allogeneic peptide–major histocompatibility complex antigens. Previous investigations have not identified T cell subsets that selectively mediate either protective immunity or pathogenic alloreactivity. We demonstrate that the small subset of peripheral T cells that naturally express two T cell receptors (TCRs) on the cell surface contributes disproportionately to aGVHD in patients after allogeneic HSCT. Dual TCR T cells from patients with aGVHD demonstrate an activated phenotype and produce pathogenic cytokines ex vivo. Dual receptor clones from a patient with symptomatic aGVHD responded specifically to mismatched recipient human leukocyte antigens (HLAs), demonstrating pathologic alloreactivity. Human dual TCR T cells are strongly activated and expanded by allogeneic stimulation in vitro, and disproportionately contribute to the repertoire of T cells recognizing both major (HLA) and minor histocompatibility antigens, providing a mechanism for their observed activity in vivo in patients with aGVHD. These results identify dual TCR T cells as a target for focused analysis of a T cell subset mediating GVHD and as a potential prognostic indicator.
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