成雙成對未必好
本文由漢氏聯(lián)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(fā)現(xiàn)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(yī)學院的研究人員發(fā)現(xiàn)在異基因HSCT后發(fā)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(chǎn)生致病性細胞因子。從一例發(fā)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(fā)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(nèi)的活動提供了解釋。這些結(jié)果證明雙TCR-T細胞是分析調(diào)節(jié)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(zhì)干細胞的免疫調(diào)節(jié)功能可以預防aGVHD的發(fā)生和減輕癥狀，在美國已經(jīng)進入到三期臨床階段。國內(nèi)也開始間充質(zhì)干細胞治療GVHD的研究，例如漢氏聯(lián)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(fā)。據(jù)初步的臨床報告，間充質(zhì)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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