Karimi Shirin, Chattopadhyay Subhasis, Chakraborty Nitya G
Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
Immunology. 2015 Feb;144(2):186-96. doi: 10.1111/imm.12387.
The most potent killing machinery in our immune system is the cytotoxic T lymphocyte (CTL). Since the possibility for self-destruction by these cells is high, many regulatory activities exist to prevent autoimmune destruction by these cells. A tumour (cancer) grows from the cells of the body and is tolerated by the body's immune system. Yet, it has been possible to generate tumour-associated antigen (TAA) -specific CTL that are also self-antigen specific in vivo, to achieve a degree of therapeutic efficacy. Tumour-associated antigen-specific T-cell tolerance through pathways of self-tolerance generation represents a significant challenge to successful immunotherapy. CD4(+) CD25(+) FoxP3(+) T cells, referred to as T regulatory (Treg) cells, are selected in the thymus as controllers of the anti-self repertoire. These cells are referred to as natural T regulatory (nTreg) cells. According to the new consensus (Nature Immunology 2013; 14:307-308) these cells are to be termed as (tTreg). There is another class of CD4(+) Treg cells also involved in regulatory function in the periphery, also phenotypically CD4(+) CD25(±) , classified as induced Treg (iTreg) cells. These cells are to be termed as peripherally induced Treg (pTreg) cells. In vitro-induced Treg cells with suppressor function should be termed as iTreg. These different Treg cells differ in their requirements for activation and in their mode of action. The current challenges are to determine the degree of specificity of these Treg cells in recognizing the same TAA as the CTL population and to circumvent their regulatory constraints so as to achieve robust CTL responses against cancer.
我们免疫系统中最强大的杀伤机制是细胞毒性T淋巴细胞（CTL）。由于这些细胞自我毁灭的可能性很高，因此存在许多调节活动来防止这些细胞引发自身免疫性破坏。肿瘤（癌症）由身体细胞生长而来，并被身体的免疫系统所耐受。然而，在体内已经能够产生肿瘤相关抗原（TAA）特异性CTL，这些CTL也是自身抗原特异性的，从而实现了一定程度的治疗效果。通过自身耐受产生途径实现的肿瘤相关抗原特异性T细胞耐受，是成功进行免疫治疗的重大挑战。CD4(+) CD25(+) FoxP3(+) T细胞，被称为T调节（Treg）细胞，在胸腺中被选择作为抗自身库的控制器。这些细胞被称为天然T调节（nTreg）细胞。根据新的共识（《自然免疫学》2013年；14:307 - 308），这些细胞应被称为（tTreg）。还有另一类CD4(+) Treg细胞也参与外周的调节功能，其表型也为CD4(+) CD25(±)，被归类为诱导性Treg（iTreg）细胞。这些细胞应被称为外周诱导性Treg（pTreg）细胞。具有抑制功能的体外诱导Treg细胞应被称为iTreg。这些不同的Treg细胞在激活要求和作用方式上存在差异。当前的挑战是确定这些Treg细胞在识别与CTL群体相同的TAA时的特异性程度，并规避它们的调节限制，以便实现针对癌症的强大CTL反应。
