成雙成對(duì)未必好
本文由漢氏聯(lián)合專家團(tuán)隊(duì)翻譯
急性移植物抗宿主病是因?yàn)樵谠煅杉?xì)胞移植過(guò)程中供者T細(xì)胞對(duì)異源肽---主要組織相容性復(fù)合體抗原的強(qiáng)烈反應(yīng)。既往的研究并未發(fā)現(xiàn)保護(hù)性免疫或病理性同種異體反應(yīng)有選擇性的T細(xì)胞亞群。華盛頓大學(xué)醫(yī)學(xué)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(xì)胞表面天然表達(dá)兩種T細(xì)胞受體（TCR）。
來(lái)自aGVHD患者的雙TCR --T細(xì)胞在體外有激活的表型，并產(chǎn)生致病性細(xì)胞因子。從一例發(fā)作期aGVHD患者得到雙受體T細(xì)胞克隆對(duì)錯(cuò)配的受者人白細(xì)胞抗原（HLA）有特異性反應(yīng)，揭示了同種異體反應(yīng)性的病理學(xué)。人雙TCR—T細(xì)胞被同種異體刺激原體外強(qiáng)烈激活和擴(kuò)增，不成比例地激發(fā)識(shí)別主要HLA和次要HLA抗原的T細(xì)胞庫(kù)，為觀察到的雙TCR—T細(xì)胞在aGVHD患者體內(nèi)的活動(dòng)提供了解釋。這些結(jié)果證明雙TCR-T細(xì)胞是分析調(diào)節(jié)GVHD的T細(xì)胞亞群重要靶點(diǎn)，并且是一個(gè)可能的預(yù)后指標(biāo)。
引申：利用間充質(zhì)干細(xì)胞的免疫調(diào)節(jié)功能可以預(yù)防aGVHD的發(fā)生和減輕癥狀，在美國(guó)已經(jīng)進(jìn)入到三期臨床階段。國(guó)內(nèi)也開(kāi)始間充質(zhì)干細(xì)胞治療GVHD的研究，例如漢氏聯(lián)合生物技術(shù)有限公司和昂賽細(xì)胞基因工程有限公司都在開(kāi)展MSC的治療應(yīng)用潛能開(kāi)發(fā)。據(jù)初步的臨床報(bào)告，間充質(zhì)干細(xì)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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