Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Front Immunol. 2021 Feb 2;11:615371. doi: 10.3389/fimmu.2020.615371. eCollection 2020.
T cell receptor (TCR) signaling influences multiple aspects of CD4 and CD8 T cell immunobiology including thymic development, peripheral homeostasis, effector subset differentiation/function, and memory formation. Additional T cell signaling cues triggered by co-stimulatory molecules and cytokines also affect TCR signaling duration, as well as accessory pathways that further shape a T cell response. Type 1 diabetes (T1D) is a T cell-driven autoimmune disease targeting the insulin producing β cells in the pancreas. Evidence indicates that dysregulated TCR signaling events in T1D impact the efficacy of central and peripheral tolerance-inducing mechanisms. In this review, we will discuss how the strength and nature of TCR signaling events influence the development of self-reactive T cells and drive the progression of T1D through effects on T cell gene expression, lineage commitment, and maintenance of pathogenic anti-self T cell effector function.
T 细胞受体 (TCR) 信号转导影响 CD4 和 CD8 T 细胞免疫生物学的多个方面，包括胸腺发育、外周稳态、效应子亚群分化/功能和记忆形成。共刺激分子和细胞因子触发的其他 T 细胞信号转导线索也会影响 TCR 信号转导的持续时间，以及进一步塑造 T 细胞反应的辅助途径。1 型糖尿病 (T1D) 是一种针对胰腺中产生胰岛素的β细胞的 T 细胞驱动的自身免疫性疾病。有证据表明，T1D 中失调的 TCR 信号事件会影响中枢和外周耐受诱导机制的功效。在这篇综述中，我们将讨论 TCR 信号事件的强度和性质如何通过对 T 细胞基因表达、谱系决定和维持致病性抗自身 T 细胞效应功能的影响，影响自身反应性 T 细胞的发育并推动 T1D 的进展。
