Wakao Hiroshi, Sugimoto Chie, Kimura Shinzo, Wakao Rika
International Epidemiology, Dokkyo Medical University, Mibu, Japan.
Office of Regulatory Science, Pharmaceutical and Medical Device Agency (PMDA), Tokyo, Japan.
Front Immunol. 2017 Dec 1;8:1711. doi: 10.3389/fimmu.2017.01711. eCollection 2017.
Although antibiotics to inhibit bacterial growth and small compounds to interfere with the productive life cycle of human immunodeficiency virus (HIV) have successfully been used to control HIV infection, the recent emergence of the drug-resistant bacteria and viruses poses a serious concern for worldwide public health. Despite intensive scrutiny in developing novel antibiotics and drugs to overcome these problems, there is a dilemma such that once novel antibiotics are launched in markets, sooner or later antibiotic-resistant strains emerge. Thus, it is imperative to develop novel methods to avoid this vicious circle. Here, we discuss the possibility of using induced pluripotent stem cell (iPSC)-derived, innate-like T cells to control infection and potential application of these cells for cancer treatment. Mucosal-associated invariant T (MAIT) cells belong to an emerging family of innate-like T cells that link innate immunity to adaptive immunity. MAIT cells exert effector functions without priming and clonal expansion like innate immune cells and relay the immune response to adaptive immune cells through production of relevant cytokines. With these characteristics, MAIT cells are implicated in a wide range of human diseases such as autoimmune, infectious, and metabolic diseases, and cancer. Circulating MAIT cells are often depleted by these diseases and often remain depleted even after appropriate remedy because MAIT cells are susceptible to activation-induced cell death and poor at proliferation , which threatens the integrity of the immune system. Because MAIT cells have a pivotal role in human immunity, supplementation of MAIT cells into immunocompromised patients suffering from severe depletion of these cells may help recapitulate or recover immunocompetence. The generation of MAIT cells from human iPSCs has made it possible to procure MAIT cells lost from disease. Such technology creates new avenues for cell therapy and regenerative medicine for difficult-to-cure infectious diseases and cancer and contributes to improvement of our welfare.
尽管用于抑制细菌生长的抗生素和干扰人类免疫缺陷病毒（HIV）复制生命周期的小分子化合物已成功用于控制HIV感染，但最近出现的耐药细菌和病毒对全球公共卫生构成了严重威胁。尽管在开发新型抗生素和药物以克服这些问题方面进行了深入研究，但仍存在一个困境，即一旦新型抗生素投放市场，迟早会出现耐药菌株。因此，开发新方法以避免这种恶性循环势在必行。在此，我们讨论使用诱导多能干细胞（iPSC）衍生的天然样T细胞来控制感染的可能性以及这些细胞在癌症治疗中的潜在应用。黏膜相关恒定T（MAIT）细胞属于一类新兴的天然样T细胞家族，它们将先天免疫与适应性免疫联系起来。MAIT细胞像先天免疫细胞一样，无需致敏和克隆扩增即可发挥效应功能，并通过产生相关细胞因子将免疫反应传递给适应性免疫细胞。具有这些特性，MAIT细胞与多种人类疾病有关，如自身免疫性疾病、感染性疾病、代谢性疾病和癌症。循环中的MAIT细胞常常因这些疾病而减少，并且即使在适当治疗后也常常仍然减少，因为MAIT细胞易受激活诱导的细胞死亡影响且增殖能力较差，这威胁到免疫系统的完整性。由于MAIT细胞在人类免疫中起关键作用，因此将MAIT细胞补充到这些细胞严重耗竭的免疫功能低下患者体内可能有助于恢复或重建免疫能力。从人类iPSC中生成MAIT细胞使得获取因疾病而丢失的MAIT细胞成为可能。这种技术为治疗难治性传染病和癌症的细胞疗法和再生医学开辟了新途径，并有助于改善我们的健康福祉。
