免疫细胞耗竭/功能障碍的概念主要是为了了解受损的 1 型免疫反应，特别是 CD8 T 细胞针对肿瘤或病毒感染细胞的反应，并已应用于其他淋巴细胞。自然杀伤 (NK) 细胞和 CD4 T 细胞支持 CD8 T 细胞的有效激活，但在肿瘤微环境和慢性病毒感染中表现出功能失调的表型。相比之下，2 型免疫细胞耗竭/功能障碍的概念尚未确立。第 2 组先天淋巴细胞 (ILC2) 和辅助性 T 2 (Th2) 细胞是主要的淋巴细胞亚群，可启动和扩大抗寄生虫免疫或过敏的 2 型免疫反应。在慢性寄生虫感染的小鼠模型中，Th2 细胞表现出受损的 2 型免疫反应。慢性气道过敏会诱导类似疲劳的 ILC2，这些 ILC2 会迅速陷入激活诱导的细胞死亡状态，以抑制过度的炎症。因此，衰竭/功能障碍的模式是多种多样的，并且取决于炎症和细胞的类型。在这篇综述中，我们总结了 1 型和 2 型免疫反应背景下淋巴细胞耗竭/功能障碍的最新知识，并讨论了慢性过敏期间 ILC2 特异性的调节机制。© 作者 2024。由牛津大学出版社代表出版日本免疫学会会员。

The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses especially by CD8 T cells against tumors or virus-infected cells and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit a dysfunctional phenotype in tumor microenvironments and in chronic virus infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy. In mouse models of chronic parasitic worm infections, Th2 cells display impaired type 2 immune responses. Chronic airway allergy induces exhausted-like ILC2s that quickly fall into activation-induced cell death to suppress exaggerated inflammation. Thus, the modes of exhaustion/dysfunction are quite diverse and rely on the types of inflammation and the cells. In this review, we summarize current knowledge of lymphocyte exhaustion/dysfunction in the context of type 1 and type 2 immune responses and discuss ILC2-specific regulatory mechanisms during chronic allergy.© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology.