Department of Internal Medicine 5 - Hematology/Oncology, University of Erlangen-Nürnberg, Erlangen, Germany.
Eur J Immunol. 2011 Mar;41(3):739-48. doi: 10.1002/eji.201040982. Epub 2011 Feb 2.
Regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance to self-antigens and are involved in modulating immune responses in autoimmunity, transplant rejection, and tumor immunity. Recently, a novel subset of TCR-αβ(+) CD4(-) CD8(-) (double negative, DN) T cells has been described to specifically suppress T-cell responses in mice. Here, we demonstrate that human DN T cells are highly potent suppressors of both CD4(+) and CD8(+) T-cell responses. In contrast to naturally occurring CD4(+) CD25(+) Tregs, DN T cells have to be activated by antigen-presenting cells (APCs) to induce their regulatory potential. The suppressive activity of DN T cells is neither mediated indirectly by modulation of APCs nor by competition for T-cell growth factors. Furthermore, DN T-cell-mediated suppression toward responder T cells is TCR dependent and requires novel protein synthesis. In contrast to murine DN T cells, which eliminate effector T cells via Fas/FasL or perforin/granzyme, human DN T cells suppress proliferation of responder T cells by cell contact-dependent mechanisms. Taken together, our data indicate that human DN T cells exert strong immunosuppressive effects on both CD4(+) and CD8(+) T cells and may serve as a new therapeutic approach to treat autoimmunity and transplant rejection.
调节性 T 细胞（Tregs）在维持对自身抗原的免疫耐受方面发挥着重要作用，并参与调节自身免疫、移植排斥和肿瘤免疫中的免疫反应。最近，人们描述了一种新型的 TCR-αβ(+) CD4(-) CD8(-)（双阴性，DN）T 细胞亚群，其特异性抑制小鼠的 T 细胞反应。在这里，我们证明人类 DN T 细胞是高度有效的 CD4(+)和 CD8(+)T 细胞反应的抑制剂。与天然存在的 CD4(+) CD25(+)Tregs 不同，DN T 细胞必须通过抗原呈递细胞（APCs）激活才能发挥其调节潜能。DN T 细胞的抑制活性既不是通过调节 APCs 间接介导的，也不是通过竞争 T 细胞生长因子介导的。此外，DN T 细胞对反应性 T 细胞的抑制作用是 TCR 依赖性的，需要新的蛋白质合成。与通过 Fas/FasL 或穿孔素/颗粒酶消除效应 T 细胞的鼠类 DN T 细胞不同，人类 DN T 细胞通过细胞接触依赖性机制抑制反应性 T 细胞的增殖。总之，我们的数据表明，人类 DN T 细胞对 CD4(+)和 CD8(+)T 细胞均具有强大的免疫抑制作用，可能成为治疗自身免疫和移植排斥的新治疗方法。
