Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, MO 63110, USA.
Int Immunol. 2023 Feb 11;35(2):67-77. doi: 10.1093/intimm/dxac050.
T cells are activated by antigen and co-stimulatory receptor signaling and undergo robust proliferation and differentiation into effector cells with protective function. Such quantitatively and qualitatively amplified T cell responses are effective in controlling acute infection and are followed by contraction of the effector population and the formation of resting memory T cells for enhanced protection against previously experienced antigens. However, in the face of persistent antigen during chronic viral infection, in autoimmunity, or in the tumor microenvironment, T cells exhibit distinct responses relative to those in acute insult in several aspects, including reduced clonal expansion and impaired effector function associated with inhibitory receptor expression, a state known as exhaustion. Nevertheless, their responses to chronic infection and tumors are sustained through the establishment of hierarchical heterogeneity, which preserves the duration of the response by generating newly differentiated effector cells. In this review, we highlight recent findings on distinct dynamics of T cell responses under "exhausting" conditions and the roles of the transcription factors that support attenuated yet long-lasting T cell responses as well as the establishment of dysfunctional states.
T 细胞通过抗原和共刺激受体信号被激活，并经历强烈的增殖和分化为具有保护功能的效应细胞。这种数量和质量上扩增的 T 细胞反应可有效控制急性感染，并随后收缩效应细胞群，形成静止的记忆 T 细胞，以增强对以前经历过的抗原的保护。然而，在慢性病毒感染、自身免疫或肿瘤微环境中，T 细胞相对于急性损伤在几个方面表现出不同的反应，包括克隆扩增减少和效应功能受损，与抑制性受体表达相关，这种状态称为衰竭。然而，它们对慢性感染和肿瘤的反应是通过建立层次异质性来维持的，这种异质性通过产生新分化的效应细胞来延长反应的持续时间。在这篇综述中，我们强调了在“衰竭”条件下 T 细胞反应的不同动态以及支持减弱但持久的 T 细胞反应的转录因子的作用，以及功能障碍状态的建立。
