来自美国圣·犹大儿童研究医院发现了一个新的信号分子，该分子能够抑制损伤身体的免疫应答。这一发现将能够有助于研究人员开发出癌症新疫苗、免疫疾病（如I型糖尿病）和炎症（如肠炎和哮喘）的新疗法。
圣·犹大的研究组发现，特化的免疫淋巴细胞——调节性T细胞释放一种由两个叫做Ebi3和Il12a的蛋白质构成的蛋白质复合体。这种蛋白质复合体如同效应器T淋巴细胞活性的一个“刹车”。这项研究的结果发表在11月22日的《自然》杂志上。
这种新的蛋白质复合体是一大类叫做细胞激素的信号分子中的一员。，细胞激素能够告诉细胞与其他细胞进行交流。由于免疫系统细胞激素白介素，因此该研究组将这种蛋白命名为白介素－35(IL-35)。大多数细胞激素通过驱动免疫攻击或导致炎症来次级免疫系统细胞。但是，IL-35则是少数的能抑制免疫系统活性的信号分子。
研究人员表示，IL-35的发现具有非常重要的意义，因为对调节型T细胞的操作是免疫治疗的一个重要目标。免疫疗法是一种通过操作免疫系统来增强或抑制其活性进而治疗感染、癌症或其他疾病的方法。尽管调节型T细胞介导的免疫疗法对具有很大的治疗潜力，但是负责细胞抑制免疫系统活性能力的分子却知之甚少，而这个问题也是阻碍该领域发展的一个重要问题。
原始出处:
Nature 450, 566-569 (22 November 2007) | doi:10.1038/nature06306; Received 31 July 2007; Accepted 26 September 2007
The inhibitory cytokine IL-35 contributes to regulatory T-cell function
Lauren W. Collison1, Creg J. Workman1, Timothy T. Kuo3, Kelli Boyd2, Yao Wang1, Kate M. Vignali1, Richard Cross1, David Sehy4, Richard S. Blumberg3 & Dario A. A. Vignali1
Department of Immunology,
Animal Resources Center, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
eBioscience, San Diego, California 92121, USA
Correspondence to: Dario A. A. Vignali1 Correspondence and requests for materials should be addressed to D.A.A.V. (Email: dario.vignali@stjude.org).
Regulatory T (Treg) cells are a critical sub-population of CD4+ T cells that are essential for maintaining self tolerance and preventing autoimmunity1, 2, for limiting chronic inflammatory diseases, such as asthma and inflammatory bowel disease3, 4, and for regulating homeostatic lymphocyte expansion5. However, they also suppress natural immune responses to parasites6 and viruses7 as well as anti-tumour immunity induced by therapeutic vaccines8. Although the manipulation of Treg function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. Here we demonstrate that Epstein-Barr-virus-induced gene 3 (Ebi3, which encodes IL-27) and interleukin-12 alpha (Il12a, which encodes IL-12/p35) are highly expressed by mouse Foxp3+ (forkhead box P3) Treg cells but not by resting or activated effector CD4+ T (Teff) cells, and that an Ebi3–IL-12 heterodimer is constitutively secreted by Treg but not Teff cells. Both Ebi3 and Il12a messenger RNA are markedly upregulated in Treg cells co-cultured with Teff cells, thereby boosting Ebi3 and IL-12 production in trans. Treg-cell restriction of this cytokine occurs because Ebi3 is a downstream target of Foxp3, a transcription factor that is required for Treg-cell development and function. Ebi3 –/– and Il12a –/– Treg cells have significantly reduced regulatory activity in vitro and fail to control homeostatic proliferation and to cure inflammatory bowel disease in vivo. Because these phenotypic characteristics are distinct from those of other IL-12 family members, this novel Ebi3–IL-12 heterodimeric cytokine has been designated interleukin-35 (IL-35). Ectopic expression of IL-35 confers regulatory activity on naive T cells, whereas recombinant IL-35 suppresses T-cell proliferation. Taken together, these data identify IL-35 as a novel inhibitory cytokine that may be specifically produced by Treg cells and is required for maximal suppressive activity.
