調節T細胞

調節T細胞regulatory T cell,Treg):是一群具有負調節機體免疫反應的淋巴細胞,通常起着維持自身耐受和避免免疫反應過度損傷機體的重要作用,但也參與腫瘤細胞逃避機體免疫監視和慢性感染。

70年代曾命名為抑制T細胞(suppressor T cell),因缺乏明確的表面標誌,研究長期處於尷尬和停頓的境地;直到90年代研究出現轉機並成為目前研究熱點,但現多稱為調節T細胞(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。

亞群

調節T細胞是免疫系統的重要組成成分,可抑制其他免疫細胞的免疫反應。這是免疫系統之中重要的「自檢」組分,可防止產生過激的免疫反應。調節T細胞有多種形式,但被了解的最透徹的是表達CD4、CD25及FOXP3調節T細胞(CD4+CD25+調節T細胞)。調節T細胞與輔助T細胞不同[1]。另一類調節T細胞亞群是Treg17細胞[2]。調節T細胞參與到成功清除入侵生物後關閉免疫反應之中,同時也防止產生自身免疫反應[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]

調節/抑制T細胞有很多種,可分為自然存在與誘導產生兩類:

自然存在:

  • CD4+ CD25+T細胞:在維持機體對自身抗原的耐受中扮演重要角色,是目前研究最廣泛深入的一種調節/抑制T細胞。

誘導產生:

  • TR1細胞:以分泌IL-10為特徵,負調節免疫應答。
  • TH3細胞: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。
  • 表達轉錄因子RORgt的調節T細胞:特異性針對腸道菌群,常見於大小腸內。在生物體內的誘導調節T細胞群體內佔到絕大部分。其誘導在新生動物體內依賴Thetis細胞。[6]

參見

參考資料

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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.