背景：黏膜相關(guān)不變性T（MAIT）細(xì)胞是半不變性T細(xì)胞，其識(shí)別高度保守的MR1分子呈遞的微生物抗原。 MAIT細(xì)胞主要位于肝臟和屏障組織中，是抗微生物防御的有效效應(yīng)物。 MAIT細(xì)胞在出生時(shí)很少，在嬰兒期約6年內(nèi)逐漸積累。 MAIT細(xì)胞的潛在細(xì)胞毒性以及它們新近描述的調(diào)節(jié)和組織修復(fù)功能，為在過(guò)繼治療中開(kāi)發(fā)其特性提供了可能性。 用作“通用”細(xì)胞的先決條件是缺乏同種反應(yīng)性潛能，這有待證明。
方法：我們使用了離體，體外和體內(nèi)模型來(lái)確定人MAIT細(xì)胞是否有助于同種異體反應(yīng)。
結(jié)果：我們表明，同種異體造血干細(xì)胞移植后MAIT細(xì)胞的恢復(fù)概括了它們?cè)趦和缙诘木徛頂U(kuò)張，而與常規(guī)T細(xì)胞的恢復(fù)無(wú)關(guān)。 在體外，同種異體細(xì)胞和細(xì)胞因子提供的信號(hào)不會(huì)誘導(dǎo)持續(xù)的MAIT細(xì)胞增殖。 在體內(nèi)，在免疫缺陷小鼠的T細(xì)胞介導(dǎo)的異種移植物抗宿主?。℅VHD）模型中，人MAIT細(xì)胞不會(huì)在組織中擴(kuò)增或積累。
結(jié)論：總而言之，這些結(jié)果提供了證據(jù)，表明MAIT細(xì)胞沒(méi)有同種反應(yīng)性潛能，并為在普遍采用的治療中克服HLA差異障礙的轉(zhuǎn)化潛能鋪平了道路。
Background: Mucosal associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of anti-microbial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as "universal" cells would be a lack of alloreactive potential, which remains to be demonstrated. Methods: We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses. Results: We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of conventional T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell mediated xenogeneic graft-versus-host disease (GVHD) in immunodeficient mice. Conclusions: Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity
doi: https:///10.1101/2021.04.29.21256184
文章來(lái)源AI翻譯，如有侵權(quán)請(qǐng)及時(shí)聯(lián)系pubpeer2016小編刪除，轉(zhuǎn)載請(qǐng)注明來(lái)源。
溫馨提示：
為方便pubmed粉絲們科研、就業(yè)等話題交流。我們根據(jù)10多個(gè)專業(yè)方向（植物、醫(yī)學(xué)、藥學(xué)、人工智能、化學(xué)、物理、財(cái)經(jīng)管理、體育等），特建立了15個(gè)國(guó)內(nèi)外博士交流群。群成員來(lái)源歐美、日韓、新加坡、清華北大、中科院等全球名校。
