Allorecognition by T Lymphocytes and Allograft Rejection.

Allorecognition by T Lymphocytes and Allograft Rejection.
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T淋巴细胞和同种异体移植排斥的同种异体认识。

DOI:
10.3389/fimmu.2016.00582
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发表时间:
2016
影响因子:
7.3
通讯作者:
Benichou G
Benichou G
中科院分区:
医学2区
文献类型:
--
作者:
Marino J;Paster J;Benichou G

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次要淋巴器官中的受体T细胞对供体抗原的识别引发适应性炎症免疫反应,导致异体移植的排斥反应。同种异体T细胞通过其T细胞受体与供体细胞上完整的同种异体主要组织相容性复合体(MHC)分子(直接途径)和/或受体抗原呈递细胞(apc)上由自身MHC分子呈递的供体肽(间接途径)相互作用而被激活。此外,最近的研究表明,同种异体MHC分子通过细胞间接触或细胞外囊泡(半直接途径)转移后,受体apc上显示的同种异体MHC分子(MHC变装)也可以被识别,从而刺激同种异体反应性T细胞。T细胞使用的特异性同种异体识别途径是由同种异体移植物的内在和外在因素决定的,可以影响同种异体反应和排斥过程的性质和程度。因此,促炎T细胞通过这些不同的途径识别不同的器官和组织,如皮肤、角膜和实体器官移植,这可能解释了为什么这些移植物以不同的方式被排斥。另一方面,抗炎调节性T细胞(Tregs)识别异体抗原并促进移植耐受的机制尚不清楚。胸腺treg可能通过间接的异体识别被激活,而外周treg则以直接的方式识别异体抗原。随着我们对促炎细胞和Treg细胞的同种异体识别机制的深入了解,正在设计新的策略来防止患者在缺乏免疫抑制药物治疗的情况下发生同种异体移植排斥反应。
Recognition of donor antigens by recipient T cells in secondary lymphoid organs initiates the adaptive inflammatory immune response leading to the rejection of allogeneic transplants. Allospecific T cells become activated through interaction of their T cell receptors with intact allogeneic major histocompatibility complex (MHC) molecules on donor cells (direct pathway) and/or donor peptides presented by self-MHC molecules on recipient antigen-presenting cells (APCs) (indirect pathway). In addition, recent studies show that alloreactive T cells can also be stimulated through recognition of allogeneic MHC molecules displayed on recipient APCs (MHC cross-dressing) after their transfer via cell–cell contact or through extracellular vesicles (semi-direct pathway). The specific allorecognition pathway used by T cells is dictated by intrinsic and extrinsic factors to the allograft and can influence the nature and magnitude of the alloresponse and rejection process. Consequently, various organs and tissues such as skin, cornea, and solid organ transplants are recognized differently by pro-inflammatory T cells through these distinct pathways, which may explain why these grafts are rejected in a different fashion. On the other hand, the mechanisms by which anti-inflammatory regulatory T cells (Tregs) recognize alloantigen and promote transplantation tolerance are still unclear. It is likely that thymic Tregs are activated through indirect allorecognition, while peripheral Tregs recognize alloantigens in a direct fashion. As we gain insights into the mechanisms underlying allorecognition by pro-inflammatory and Treg cells, novel strategies are being designed to prevent allograft rejection in the absence of ongoing immunosuppressive drug treatment in patients.
DOI: 10.2217/imt.11.2
发表时间: 2011-06
期刊: Immunotherapy
影响因子: 2.8
作者:
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发表时间: 2009-01-15
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影响因子: --
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发表时间: 2010-04-15
期刊: BLOOD
影响因子: 20.3
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DOI: 10.1073/pnas.90.8.3373
发表时间: 1993-04-15
影响因子: 11.1
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AUCHINCLOSS, H;LEE, R;GLIMCHER, LH
通讯作者: GLIMCHER, LH