CTLA4 的协同抑制作用
中文名称
通路描述
CTLA-4（细胞毒性 T 淋巴细胞抗原 4）主要表达在活化的 T 细胞和调节性 T 细胞（Treg）表面。它在抑制 T 细胞激活和维持免疫稳态中起关键作用（Alegre 等，2001）。T 细胞抗原受体（TCR）激活后诱导 CTLA-4 表达。CTLA-4 与 TCR 激活结合通过两种主要机制抑制 T 细胞反应：与 CD28 竞争 B7 结合以减少共刺激，并直接向 T 细胞传递负信号。据报道，SHP-2 磷酸酶在 CTLA-4 上的磷酸酪氨酸依赖性招募抑制 T 细胞激活和扩增，通过磷酸化 CD3/TCR 链的去磷酸化实现。CTLA-4 通过多种机制抑制 T 细胞激活，包括减少 IL-2 的产生和表达，以及通过阻滞 T 细胞进入细胞周期的 G1 期（Greenwald 等，2002）。作为检查点分子，CTLA-4 不仅影响表达它的 T 细胞，还对其他 T 细胞的增殖发挥主导的调节作用。限制周围 T 细胞增殖的能力对于防止自身反应性和维持免疫耐受至关重要，确保免疫系统不会无意识地靶向身体自身组织。由于其调节免疫反应的能力，CTLA-4 已成为管理癌症、自身免疫疾病和移植排斥等条件的重要治疗靶点（Tivol 等，1995，Chambers 等，1997，Rudd 和 Schneider 2003）。
英文描述
Co-inhibition by CTLA4 Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule predominantly expressed on the surface of activated T cells and regulatory T (Treg) cells. It plays a critical role in inhibiting T-cell activation and maintaining immune homeostasis (Alegre et al. 2001). After acctivation of T lymphocytes through their antigen receptor (TCR) induces the upregulation of CTLA-4 expression. CTLA-4 engagement alongside TCR activation inhibits T cell responses through two primary mechanisms: competing with CD28 for B7 binding to reduce costimulation, and delivering a negative signal directly into the T cells. It has been reported that phosphotyrosine-dependent recruitment of the SHP-2 phosphatase to CTLA-4 inhibits T cell activation and expansion by dephosphorylation of CD3/TCR chains.
CTLA-4 inhibits T cell activation through several mechanisms, including the reduction of IL-2 production and expression, as well as by arresting T cells in the G1 phase of the cell cycle (Greenwald et al. 2002). This checkpoint molecule not only impacts the T cells that express it but also exerts a dominant regulatory influence on the proliferation of other T cells. This ability to limit the proliferation of surrounding T cells is crucial in preventing autoreactivity and maintaining immune tolerance, ensuring that the immune system does not inadvertently target the body's own tissues.
Due to its ability to modulate immune responses, CTLA-4 has emerged as a significant therapeutic target for managing conditions such as cancer, autoimmune diseases, and transplant rejection (Tivol et al. 1995, Chambers et al. 1997, Rudd and Schneider 2003).
CTLA-4 inhibits T cell activation through several mechanisms, including the reduction of IL-2 production and expression, as well as by arresting T cells in the G1 phase of the cell cycle (Greenwald et al. 2002). This checkpoint molecule not only impacts the T cells that express it but also exerts a dominant regulatory influence on the proliferation of other T cells. This ability to limit the proliferation of surrounding T cells is crucial in preventing autoreactivity and maintaining immune tolerance, ensuring that the immune system does not inadvertently target the body's own tissues.
Due to its ability to modulate immune responses, CTLA-4 has emerged as a significant therapeutic target for managing conditions such as cancer, autoimmune diseases, and transplant rejection (Tivol et al. 1995, Chambers et al. 1997, Rudd and Schneider 2003).
所含基因
21 个基因