Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Immunol Med. 2023 Mar;46(1):1-8. doi: 10.1080/25785826.2022.2129370. Epub 2022 Oct 11.
CD4 T lymphocytes play an essential role in adaptive immune responses. In pathogen infection, naïve CD4 T cells that strongly respond to foreign antigens robustly proliferate to differentiate into effector/memory cells, contributing to elimination of the pathogen concerned. In addition to this conventional T cell activation pathway, naïve T cells can also weakly respond to self antigens in the periphery to spontaneously acquire a memory phenotype through homeostatic proliferation in steady state. Such 'memory-phenotype' (MP) CD4 T lymphocytes are distinguishable from foreign antigen-specific memory cells in terms of marker expression. Once generated, MP cells are maintained by rapid proliferation while differentiating into the T-bet 'MP1' subset, with the latter response promoted by IL-12 homeostatically produced by type 1 dendritic cells. Importantly, MP1 cells possess innate immune function; they can produce IFN-γ in response to IL-12 and IL-18 to contribute to host defense against pathogens. Similarly, the presence of RORγt 'MP17' and Gata3 'MP2' cells as well as their potential immune functions have been proposed. In this review, I will discuss our current understanding on the unique mechanisms of generation, maintenance, and differentiation of MP CD4 T lymphocytes as well as their functional significance in various disease conditions.
CD4 T 淋巴细胞在适应性免疫反应中发挥着至关重要的作用。在病原体感染中，强烈响应外来抗原的初始 CD4 T 细胞会大量增殖，分化为效应/记忆细胞，有助于消除相关病原体。除了这种传统的 T 细胞激活途径外，初始 T 细胞还可以在外周组织中微弱地响应自身抗原，通过在稳态下的自身增殖，自发获得记忆表型。这种“记忆表型”（MP）CD4 T 淋巴细胞在标记表达方面与特异性识别外来抗原的记忆细胞不同。一旦产生，MP 细胞通过快速增殖来维持自身，同时分化为 T-bet“MP1”亚群，后者的反应受到 1 型树突状细胞稳态产生的 IL-12 的促进。重要的是，MP1 细胞具有先天免疫功能；它们可以在 IL-12 和 IL-18 的刺激下产生 IFN-γ，有助于宿主抵抗病原体。类似地，已经提出了存在 RORγt“MP17”和 Gata3“MP2”细胞及其潜在的免疫功能。在这篇综述中，我将讨论我们目前对 MP CD4 T 淋巴细胞的生成、维持和分化的独特机制以及它们在各种疾病状态下的功能意义的理解。
