Trogocytosis as a mechanistic link between chimerism and prenatal tolerance.
Trogocytosis as a mechanistic link between chimerism and prenatal tolerance.
复制标题
DOI：
10.4161/chim.26666
复制
发表时间：
2013-10-01
期刊：
影响因子：
--
通讯作者：
Shaaban, Aimen F
中科院分区：
文献类型：
--
作者：
Alhajjat, Amir M;Strong, Beverly S;Shaaban, Aimen F
子宫内造血细胞移植（IUHCT）对于治疗镰状细胞病、免疫缺陷疾病和遗传性代谢紊乱等先天性细胞功能障碍疾病具有很大的希望。然而，不涉及免疫缺陷疾病的IUHCT临床病例的反复失败迫使对胎儿免疫系统进行更仔细的检查。虽然以前已经研究了调节T细胞耐受的机制，但在产前嵌合体中导致NK细胞耐受的教育机制仍然未知。由于诱导和维持这种耐受性需要低水平的供体细胞（1.8%），因此这些机制可能采用间接的宿主-供体相互作用。本报告探讨了在产前嵌合体中，供体到宿主的MHC转移（trogocytosis）作为调节NK细胞耐受性发展和维持的内在机制。研究结果表明，表型耐受的宿主NK细胞在发育过程中表达低水平的转移供体MHC抗原，后来成为成熟的细胞毒性淋巴细胞。在产前嵌合体中，移植供体MHC配体的顺式识别如何影响耐受性NK细胞的选择和维持，还需要进一步的研究。
In utero hematopoietic cellular transplantation (IUHCT) holds great promise for the treatment of congenital diseases of cellular dysfunction such as sickle cell disease, immunodeficiency disorders and inherited metabolic disorders. However, repeated failures in clinical cases of IUHCT that do not involve an immunodeficiency disease force a closer examination of the fetal immune system. While the mechanisms regulating T cell tolerance have been previously studied, the educational mechanisms leading to NK cell tolerance in prenatal chimeras remain unknown. As a low level of donor cells (1.8%) is required to induce and maintain this tolerance, it is likely that these mechanisms employ indirect host-donor interaction. This report examines donor-to-host MHC transfer (trogocytosis) as an intrinsic mechanism regulating the development and maintenance of NK cell tolerance in prenatal chimeras. The findings demonstrate that phenotypically tolerant host NK cells express low levels of transferred donor MHC antigens during development and later as mature cytotoxic lymphocytes. Further study is needed to understand how the cis-recognition of transferred donor MHC ligand influences the selection and maintenance of tolerant NK cells in prenatal chimeras.