目前器官移植中常面臨的一個(gè)問(wèn)題是身體會(huì)“認(rèn)生”,，即免疫系統(tǒng)會(huì)對(duì)移植器官產(chǎn)生排異反應(yīng),。英國(guó)研究人員報(bào)告說(shuō)找到了一種讓免疫系統(tǒng)和移植器官提前變成“熟人”的辦法，能減少器官移植中的排異反應(yīng),。
英國(guó)牛津大學(xué)等機(jī)構(gòu)的研究人員在美國(guó)新一期《科學(xué)—轉(zhuǎn)化醫(yī)學(xué)》（Science Translational Medicine）上報(bào)告說(shuō),，在這個(gè)過(guò)程中起關(guān)鍵作用的是一種名為調(diào)節(jié)性T細(xì)胞的免疫細(xì)胞。這種細(xì)胞具有降低免疫反應(yīng)的功能,。領(lǐng)導(dǎo)研究的安德魯·布謝爾介紹說(shuō),，免疫系統(tǒng)就像是一支與病毒等外來(lái)入侵者作戰(zhàn)的軍隊(duì)，但當(dāng)戰(zhàn)爭(zhēng)結(jié)束后,，總要有人來(lái)告訴士兵們停止開(kāi)火,，對(duì)免疫系統(tǒng)而言調(diào)節(jié)性T細(xì)胞就起著這樣的作用。
因此,，研究人員想到可以讓調(diào)節(jié)性T細(xì)胞提前“認(rèn)識(shí)”將要移植的器官,，這樣它就可以通知免疫系統(tǒng)不再發(fā)動(dòng)攻擊。研究人員對(duì)實(shí)驗(yàn)鼠進(jìn)行了血管移植,，并提前從要移植的血管中提取出一些細(xì)胞,，將它們和一些調(diào)節(jié)性T細(xì)胞在特定條件下共同培養(yǎng)，在這些細(xì)胞彼此“熟悉”后,，再將調(diào)節(jié)性T細(xì)胞注入進(jìn)行血管移植的實(shí)驗(yàn)鼠體內(nèi),，果然成功減少了排異反應(yīng)。
布謝爾說(shuō),，現(xiàn)在一些不同的研究小組正在探索培養(yǎng)調(diào)節(jié)性T細(xì)胞的不同方式,，今后相關(guān)領(lǐng)域中的一個(gè)關(guān)注點(diǎn)將是比較哪種方式最有效,，能最大程度減少器官移植中的排異反應(yīng)。（生物谷Bioon.com）
生物谷推薦原文：
Science Translational Medicine DOI： 10.1126/scitranslmed.3002099
Functional Regulatory T Cells Produced by Inhibiting Cyclic Nucleotide Phosphodiesterase Type 3 Prevent Allograft Rejection
Feng, Gang; Nadig, Satish N.; B?ckdahl, Liselotte; Beck, Stephan; Francis, Ross S.; Schiopu, Alexandru; Whatcott, Andrew; Wood, Kathryn J.; Bushell, Andrew
Regulatory T cells (Tregs) manipulated ex vivo have potential as cellular therapeutics in autoimmunity and transplantation. Although it is possibleto expand naturally occurring Tregs, an attractive alternative possibility, particularly suited to solid organ and bone marrow transplantation, is the stimulationof total T cell populations with defined allogeneic antigen-presenting cells (APCs) under conditions that lead to the generationor expansion of donor-reactive, adaptive Tregs. Here we demonstrate that stimulation of mouse CD4+ T cells by immature allogeneic dendritic cells combined with pharmacological inhibition of phosphodiesterase 3 (PDE) resultedin a functional enrichment of Foxp3+ T cells. Without further manipulation or selection, the resultant population delayed skin allograft rejection mediated bypolyclonal CD4+ effectors or donor-reactive CD8+ T cell receptor transgenic T cells and inhibited both effector cell proliferation and T cell priming for interferon-γ production.Notably, PDE inhibition also enhanced the enrichment of human Foxp3+ CD4+ T cells driven by allogeneic APCs. These cells inhibited T cell proliferation in a standard in vitro mixed lymphocyte assayand, moreover, attenuated the development of vasculopathy mediated by autologous peripheral blood mononuclear cells in a functionallyrelevant humanized mouse transplant model. These data establish a method for the ex vivo generation of graft-reactive, functionalmouse and human Tregs that uses a clinically approved agent, making pharmacological PDE inhibition a potential strategy for Treg-based therapies.
