《Nature》细胞毒性T细胞不为人知的新特征

　　

生物通报道，耶鲁大学医学院免疫学系，哈佛大学医学院儿童医院的科学家最近发现了免疫细胞细胞毒性T细胞的一个新特征，相关成果文章CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help发表在最近一期的Nature杂志上。

 

细胞毒性CD8+T淋巴细胞（CTL），是T淋巴细胞群中部分具有杀伤活性的细胞，在机体细胞免疫中发挥着重要的作用，特别是住抗病毒、抗细胞内细菌和抗肿瘤细胞中作用尤为突出。

 

细胞毒性CD8+T淋巴细胞通过TCRαβ识别靶细胞特异性抗原：MHC I类分子复合物。Th细胞对CTL活化的辅助作用需要两个特异性的T细胞同时结合于一个抗原提呈细胞（APC）上，然后通过以下两种途径完成：（1）活化的Th通过表面表达的CD40配体（CD40L）与表达于APC表而的CD40结合，活化APC，使其表达协同刺激分子，如B7等，后者使CTL得到协同刺激信号，自分泌IL-2等成分，允分活化，进行增值； （2）未活化的Th细胞可与APC表面表达的少量协同刺激分子结合得到活化，通过旁分泌的方式分泌IL-2，使相邻的CTL得到活化。

 

CD4+T细胞对细胞毒性CD8+T细胞的活化以及记忆具有重要的作用。然而，耶鲁和哈佛大学的研究者Nakanishi等人，发现CD4+T细胞的一个新功能。

 

CD4+ T细胞是将CD8+ T细胞吸引到病毒感染的粘膜点所需要的因子。CD4+ T细胞的帮助需要干扰素-γ的分泌和局部趋化因子分泌的诱导。这些研究结果为理解细胞免疫机制提供了新的理论依据。

（生物通 小茜）

生物通推荐原文检索

CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help

Yusuke Nakanishi1, Bao Lu2, Craig Gerard2 & Akiko Iwasaki1

 

Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA

Pulmonary Division, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Akiko Iwasaki1 Correspondence and requests for materials should be addressed to A.I. (Email: [e-mail]).

 

【Abstract】

CD4+ T helper cells are well known for their role in providing critical signals during priming of cytotoxic CD8+ T lymphocyte (CTL) responses in vivo. T-cell help is required for the generation of primary CTL responses as well as in promoting protective CD8+ memory T-cell development1. However, the role of CD4 help in the control of CTL responses at the effector stage is unknown. Here we show that fully helped effector CTLs are themselves not self-sufficient for entry into the infected tissue, but rely on the CD4+ T cells to provide the necessary cue. CD4+ T helper cells control the migration of CTL indirectly through the secretion of IFN- and induction of local chemokine secretion in the infected tissue. Our results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells.