成雙成對未必好
本文由漢氏聯合專家團隊翻譯
急性移植物抗宿主病是因為在造血干細胞移植過程中供者T細胞對異源肽---主要組織相容性復合體抗原的強烈反應。既往的研究并未發現保護性免疫或病理性同種異體反應有選擇性的T細胞亞群。華盛頓大學醫學院的研究人員發現在異基因HSCT后發生aGVHD患者一小部分外周血T細胞表面天然表達兩種T細胞受體（TCR）。
來自aGVHD患者的雙TCR --T細胞在體外有激活的表型，并產生致病性細胞因子。從一例發作期aGVHD患者得到雙受體T細胞克隆對錯配的受者人白細胞抗原（HLA）有特異性反應，揭示了同種異體反應性的病理學。人雙TCR—T細胞被同種異體刺激原體外強烈激活和擴增，不成比例地激發識別主要HLA和次要HLA抗原的T細胞庫，為觀察到的雙TCR—T細胞在aGVHD患者體內的活動提供了解釋。這些結果證明雙TCR-T細胞是分析調節GVHD的T細胞亞群重要靶點，并且是一個可能的預后指標。
引申：利用間充質干細胞的免疫調節功能可以預防aGVHD的發生和減輕癥狀，在美國已經進入到三期臨床階段。國內也開始間充質干細胞治療GVHD的研究，例如漢氏聯合生物技術有限公司和昂賽細胞基因工程有限公司都在開展MSC的治療應用潛能開發。據初步的臨床報告，間充質干細胞的治療都取得很明顯療效，部分患者擺脫了大量使用藥物的困擾。
原文摘選：
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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