Chen WanJun, Wahl Sharon M
Cellular Immunology Section, Oral Infection and Immunity Branch, NIDCR, NIH, Room 332, Building 30, Bethesda, MD 20892-4352, USA.
Cytokine Growth Factor Rev. 2003 Apr;14(2):85-9. doi: 10.1016/s1359-6101(03)00003-0.
A unique population of CD4(+) T lymphocytes that constitutively express CD25 has been recognized as anergic/suppressor cells. While the immunosuppressive activity of these CD4(+)CD25(+) cells has been validated and implicated in tolerance, autoimmunity, transplantation, cancer and infectious diseases, the mechanism(s) by which they function still remains controversial. Although the involvement of TGF-beta was initially discounted, emerging evidence now links this cytokine with CD4(+)CD25(+) T cell-mediated suppression of antigen-activated T cells. In this perspective, we summarize recently published studies, as well as our own data, which shed light on how cell membrane-bound TGF-beta can deliver a regulatory signal to target cells via a contact-dependent process. Moreover, suppressor T cell function is a complex process, tightly regulated by multiple factors, including IL-2, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and glucocorticoid induced TNF receptor (GITR). Collectively, multiple previously unconnected puzzle pieces are beginning to be linked into a more coherent, albeit incomplete picture of CD4(+)CD25(+) T cell-mediated suppression.
一群组成性表达CD25的独特CD4(+) T淋巴细胞已被认定为无反应性/抑制性细胞。虽然这些CD4(+)CD25(+)细胞的免疫抑制活性已得到验证，并与耐受性、自身免疫、移植、癌症和传染病有关，但其发挥作用的机制仍存在争议。尽管最初认为转化生长因子-β（TGF-β）不参与其中，但新出现的证据现在将这种细胞因子与CD4(+)CD25(+) T细胞介导的对抗原激活T细胞的抑制联系起来。从这个角度来看，我们总结了最近发表的研究以及我们自己的数据，这些研究揭示了细胞膜结合的TGF-β如何通过接触依赖过程向靶细胞传递调节信号。此外，抑制性T细胞功能是一个复杂的过程，受到多种因素的严格调控，包括白细胞介素-2（IL-2）、细胞毒性T淋巴细胞相关抗原-4（CTLA-4）和糖皮质激素诱导的肿瘤坏死因子受体（GITR）。总的来说，多个以前未关联的拼图碎片开始被拼凑成一幅更连贯、尽管仍不完整的CD4(+)CD25(+) T细胞介导的抑制图景。
