Memory T cells in organ transplantation: progress and challenges.
Memory T cells in organ transplantation: progress and challenges.
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DOI：
10.1038/nrneph.2016.9
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Kirk AD
中科院分区：
文献类型：
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作者：
Espinosa JR;Samy KP;Kirk AD
抗原经历的T细胞，也称为记忆T细胞，在功能上和表型上不同于幼稚T细胞。它们增强的粘附分子表达和减少的共刺激需求使它们能够对随后的抗原遭遇产生有效和快速的回忆反应。记忆T细胞产生的响应于先前的抗原暴露可以与其他不相同，但类似的抗原交叉反应。这种异源交叉反应性不仅增强了保护性免疫应答，而且还产生了从头同种免疫。后一种特征越来越被认为是同种异体移植物接受的潜在障碍，值得免疫干预，并且已经研究了几种方法。钙调磷酸酶抑制剂有效地控制记忆T细胞对同种异体移植物的反应，但这种益处是以增加感染发病率为代价的。淋巴细胞耗竭消除了同种异体特异性T细胞，但在一定程度上保留了记忆T细胞，使得患者不会完全失去保护性免疫。相对于钙调磷酸酶抑制，共刺激阻断与降低的副作用特征和改善的移植物功能相关，但在控制记忆T细胞应答方面缺乏功效。靶向在记忆T细胞上上调的粘附分子可能提供额外的手段来控制抗共刺激阻断的记忆T细胞反应。
Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens. This heterologous cross-reactivity not only enhances protective immune responses, but also engenders de novo alloimmunity. This latter characteristic is increasingly recognized as a potential barrier to allograft acceptance that is worthy of immunotherapeutic intervention, and several approaches have been investigated. Calcineurin inhibition effectively controls memory T-cell responses to allografts, but this benefit comes at the expense of increased infectious morbidity. Lymphocyte depletion eliminates allospecific T cells but spares memory T cells to some extent, such that patients do not completely lose protective immunity. Co-stimulation blockade is associated with reduced adverse-effect profiles and improved graft function relative to calcineurin inhibition, but lacks efficacy in controlling memory T-cell responses. Targeting the adhesion molecules that are upregulated on memory T cells might offer additional means to control co-stimulation-blockade-resistant memory T-cell responses.