Graft-Derived Reconstitution of Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation
Graft-Derived Reconstitution of Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation
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DOI：
10.1016/j.bbmt.2017.10.003
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发表时间：
2018-02-01
影响因子：
4.3
通讯作者：
Turtle, Cameron J.
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Abir;Hanafi, Laila-Aicha;Turtle, Cameron J.
粘膜相关不变T（MAIT）细胞表达半不变V α 7.2（+）T细胞受体（TCR），其识别来自不同细菌和真菌物种的配体。在新生儿中，MAIT细胞增殖与胃肠道（GI）细菌定植一致。相反，在非炎症条件下，由于TCR信号的获得性调节，成人MAIT细胞保持静止。尚未描述异基因造血细胞移植（HCT）后炎症和改变的GI微生物群对MAIT细胞重建的影响。我们在清髓性（n = 41）和非清髓性（n = 66）异基因HCT受者中进行了MAIT细胞重建的观察性研究，发现尽管在HCT后30天MAIT细胞数量迅速和早期增加至平台，但至少1年内MAIT细胞数量未能正常化。脐带血移植受者和HCT后接受环磷酰胺预防移植物抗宿主病（GVHD）的受者MAIT细胞重建严重受损。从HCT移植物分离的MAIT细胞和HCT后受体血液之间的TCR β基因序列的共享表明，早期MAIT细胞重建至少部分是由于在HCT移植物中转移的MAIT细胞的增殖。TCR依赖性MAIT细胞增殖需要炎性细胞因子，表明细菌V α 7.2（+）TCR配体可能促进HCT后MAIT细胞重建。稳健的MAIT细胞重建与布劳特氏菌属的GI丰度增加相关。MAIT细胞抑制常规T细胞的增殖，这与可能的调节作用一致。我们的数据确定了影响MAIT细胞重建的可改变因素，这些因素可能影响HCT后GVHD的风险。(C)2017年美国血液和骨髓移植协会。
Mucosal-associated invariant T (MAIT) cells express a semi-invariant V alpha 7.2(+) T cell receptor (TCR) that recognizes ligands from distinct bacterial and fungal species. In neonates, MAIT cells proliferate coincident with gastrointestinal (GI) bacterial colonization. In contrast, under noninflammatory conditions adult MAIT cells remain quiescent because of acquired regulation of TCR signaling. Effects of inflammation and the altered GI microbiota after allogeneic hematopoietic cell transplantation (HCT) on MAIT cell reconstitution have not been described. We conducted an observational study of MAIT cell reconstitution in myeloablative (n = 41) and nonmyeloablative (n = 66) allogeneic HCT recipients and found that despite a rapid and early increase to a plateau at day 30 after HCT, MAIT cell numbers failed to normalize for at least 1 year. Cord blood transplant recipients and those who received post-HCT cyclophosphamide for graft versus host disease (GVHD) prophylaxis had profoundly impaired MAIT cell reconstitution. Sharing of TCR beta gene sequences between MAIT cells isolated from HCT grafts and blood of recipients after HCT showed early MAIT cell reconstitution was due at least in part to proliferation of MAIT cells transferred in the HCT graft. Inflammatory cytokines were required for TCR-dependent MAIT cell proliferation, suggesting that bacterial V alpha 7.2(+) TCR ligands might promote MAIT cell reconstitution after HCT. Robust MAIT cell reconstitution was associated with an increased GI abundance of Blautia spp. MAIT cells suppressed proliferation of conventional T cells consistent with a possible regulatory role. Our data identify modifiable factors impacting MAIT cell reconstitution that could influence the risk of GVHD after HCT. (C) 2017 American Society for Blood and Marrow Transplantation.