PNAS：调节性T细胞使免疫系统放过肿瘤

生物谷

科研人员通过研究健康人群的免疫系统发现，有两种细胞的相互作用可能有助于解释为什么机体的自然防御系统未能识别和战胜肿瘤。该研究成果发表在新一期的《美国国家科学院院刊》上。“这无疑为治疗癌症和开发新的靶向药物提供了新的方向”，该试验的领导者伦敦大学国王学院免疫学家LeonieTaams说。

调节性T细胞能保持免疫系统的稳定，主要控制引起炎症的巨噬细胞，炎症是机体对付感染的第一反应。正是由于调节性T细胞阻止了杀伤性T细胞对肿瘤发动的袭击，它们也能“幽禁”巨噬细胞从而抑制炎症和机体对肿瘤的“监视”。调节性T细胞可迷惑免疫系统，即使肿瘤发生也装作若无其事。科学家早就知道细菌等微生物能刺激巨噬细胞，但其功能如何被封闭依然是个谜。

虽然该研究在健康人群中进行，但对于治疗癌症也具有一定的意义，Taams认为，调节性T细胞确实是在发挥作用，但不是在正确的时间和地点。因此，从肿瘤组织中移除调节性T细胞或许对治疗更有效。（医药经济报）

原始出处:

Published online before print October 17, 2007, 10.1073/pnas.0708426104
PNAS | October 23, 2007 | vol. 104 | no. 43 | 17034-17039

Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes

Hayley G. Evans*, Tesha Suddason ${dagger}$ , Ian Jackson ${dagger}$ , Leonie S. Taams*, ${ddagger}$ , and Graham M. Lord ${dagger}$ , ${ddagger}$ , $§$ ,¶

Departments of *Immunobiology and ${dagger}$ Nephrology and Transplantation, King's College London, London SE1 9RT, United Kingdom; $§$ Harvard School of Public Health, Harvard University, Boston, MA 02115; and ¶National Institute for Health Research Biomedical Research Centre, Guy's and St. Thomas' Hospital and King's College London, London SE1 9RT, United Kingdom

Communicated by Laurie H. Glimcher, Harvard Medical School, Boston, MA, September 5, 2007 (received for review August 1, 2007)

Recently, a new lineage of CD4+ T cells has been described in the mouse that specifically secretes IL-17 [T helper (Th) 17]. This discovery has led to a revision of the hypothesis that many autoimmune diseases are predominantly a Th1 phenomenon and may instead be critically dependent on the presence of Th17 cells. Murine Th17 cells differentiate from naïve T cell precursors in the presence of TGF- $beta$ and IL-6 or IL-21. However, given their putative importance in human autoimmunity, very little is known about the pathways that control the expression of IL-17 in humans. Here we show that the factors that determine the expression of IL-17 in human CD4+ T cells are completely different from mice. IL-6 and IL-21 were unable to induce IL-17 expression in either naïve or effector T cells, and TGF- $beta$ actually inhibited IL-17 expression. The expression of IL-17 was maximally induced from precommitted precursors present in human peripheral blood by cell–cell contact with Toll-like receptor-activated monocytes in the context of T cell receptor ligation. Furthermore, unlike IFN- ${gamma}$ , IL-17 expression was not suppressed by the presence of FOXP3+ regulatory CD4+ T cells. Taken together, these data indicate that human and mouse Th17 cells have important biological differences that may be of critical importance in the development of therapeutic interventions in diseases characterized by aberrant T cell polarization.