Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA.
Front Oncol. 2012 Sep 19;2:119. doi: 10.3389/fonc.2012.00119. eCollection 2012.
There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged "self," such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to "self" moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.
有确凿的证据表明，淋巴细胞是辐射损伤正常组织中反复出现的特征，但评估其功能意义一直很困难。在组织发病机制和保护中都假设了矛盾的作用，尽管这些作用不一定相互排斥，因为免疫系统在任何时候都可能表现出看似对立的一面。虽然 T 淋巴细胞在辐射损伤正常组织反应中的确切作用可能仍然不清楚，但它们在组织损伤后积累表明它们可能是放射治疗干预的关键靶点，值得进一步研究。最近的发现进一步强调了这一点，即病理损伤的“自身”，如暴露于电离辐射后发生的情况，可以产生具有激活与激活病原体适应性免疫相似途径的危险信号。此外，证明具有识别“自身”部分的识别雷达的 T 细胞亚群已经彻底改变了我们对所有免疫反应如何受到控制和调节的看法。基于不同免疫细胞亚群之间免疫功能的分离，产生了新的自身免疫概念。不言而喻，免疫系统具有调节辐射诱导的组织损伤的能力，从再生失败到纤维化，再到急性和慢性晚期效应，甚至致癌作用。我们对 T 淋巴细胞与辐射损伤组织之间相互作用的理解可能仍然很初步，但现在是重新审视它们的潜在作用、它们的放射生物学和微环境影响以及治疗干预的可能性的好时机。这篇综述将讨论 T 细胞反应在辐射暴露背景下的阴阳两面，它们如何驱动或保护正常组织副作用，以及我们可能对此做些什么。
