调节T细胞
调节T细胞(regulatory T cell,Treg):是一群具有负调节机体免疫反应的淋巴细胞,通常起着维持自身耐受和避免免疫反应过度损伤机体的重要作用,但也参与肿瘤细胞逃避机体免疫监视和慢性感染。
70年代曾命名为抑制T细胞(suppressor T cell),因缺乏明确的表面标志,研究长期处于尴尬和停顿的境地;直到90年代研究出现转机并成为目前研究热点,但现多称为调节T细胞(regulatory T cell)。
調節性T細胞最重要的分子標記是一種轉錄因子Foxp3,在所有調節性T細胞中均可發現有多量表現。
亚群
调节T细胞是免疫系统的重要组成成分,可抑制其他免疫细胞的免疫反應。这是免疫系统之中重要的“自检”组分,可防止产生过激的免疫反應。调节T细胞有多种形式,但被了解的最透彻的是表达CD4、CD25及FOXP3调节T细胞(CD4+CD25+调节T细胞)。调节T细胞与辅助T细胞不同[1]。另一类调节T细胞亚群是Treg17细胞[2]。调节T细胞参与到成功清除入侵生物后关闭免疫反應之中,同时也防止产生自身免疫反應[3]。
CD4+ Foxp3+ CD25(high) regulatory T cells have been called "naturally occurring" regulatory T cells[4] to distinguish them from "suppressor" T cell populations that are generated in vitro. Additional regulatory T cell populations include Tr1, Th3, CD8+CD28-, and Qa-1 restricted T cells. The contribution of these populations to self-tolerance and immune homeostasis is less well defined. Foxp3 can be used as a good marker for mouse CD4+CD25+ T cells, although recent studies have also shown evidence for Foxp3 expression in CD4+CD25- T cells. In humans, Foxp3 is also expressed by recently activated conventional T-cells and thus does not specifically identify human Tregs.[5]
调节/抑制T细胞有很多种,可分為自然存在與誘導產生兩類:
自然存在:
- CD4+ CD25+T细胞:在维持机体对自身抗原的耐受中扮演重要角色,是目前研究最广泛深入的一种调节/抑制T细胞。
誘導產生:
- TR1细胞:以分泌IL-10为特征,负调节免疫应答。
- TH3细胞:最早在口服免疫耐受性動物模型中發現,以分泌轉化生長因子-β(TGF-β)作為其功能性細胞激素。研究顯示可能與口服免疫耐受性、黏膜免疫機制有關。
- 表达转录因子RORgt的调节T细胞:特异性针对肠道菌群,常见于大小肠内。在生物体内的诱导调节T细胞群体内占到绝大部分。其诱导在新生动物体内依赖Thetis细胞。[6]
參見
参考资料
- ^ Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. February 2003, 299 (5609): 1057–61. Bibcode:2003Sci...299.1057H. PMID 12522256. doi:10.1126/science.1079490.
- ^ Singh B, Schwartz JA, Sandrock C, Bellemore SM, Nikoopour E. Modulation of autoimmune diseases by interleukin (IL)-17 producing regulatory T helper (Th17) cells. The Indian Journal of Medical Research. November 2013, 138 (5): 591–4. PMC 3928692
. PMID 24434314.
- ^ Shevach EM. Regulatory T cells in autoimmmunity*. Annual Review of Immunology. 2000, 18: 423–49. PMID 10837065. doi:10.1146/annurev.immunol.18.1.423.
- ^ Schmetterer, Klaus G.; Neunkirchner, Alina; Pickl, Winfried F. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. The FASEB Journal. June 2012, 26 (6): 2253–2276. ISSN 0892-6638. PMID 22362896. doi:10.1096/fj.11-193672.
- ^ Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annual Review of Immunology. 2004, 22: 531–62. PMID 15032588. doi:10.1146/annurev.immunol.21.120601.141122.
- ^ Akagbosu, B. Novel antigen-presenting cell imparts T(reg)-dependent tolerance to gut microbiota.. Nature. 2022, 610: 752–60. PMID 36070798. doi:10.1038/s41586-022-05309-5.
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