近日,，來自英國伯明翰大學(xué)醫(yī)學(xué)學(xué)院的研究人員發(fā)現(xiàn),，IL-21能夠抑制T細胞產(chǎn)生IL-2，以此影響了調(diào)節(jié)性T細胞（Treg）的體內(nèi)平衡,。相關(guān)研究于5月17日發(fā)表在Blood上,。
Treg是一類具有負調(diào)節(jié)作用的T細胞亞群，包括在胸腺內(nèi)分化而成的自然調(diào)節(jié)T細胞(如CD4+CD25+T細胞)和在胸腺外誘導(dǎo)產(chǎn)生的適應(yīng)性調(diào)節(jié)T細胞(如Tr1細胞和Th3細胞),。調(diào)整Treg的負調(diào)節(jié)作用,，對疫苗的開發(fā)，腫瘤監(jiān)測的有效性,，以及自身免疫的發(fā)生都具有重要意義,。
之前的研究就已經(jīng)發(fā)現(xiàn)，細胞因子IL-21能夠妨礙Treg的負調(diào)節(jié)作用,。然而,，這是否能夠反映出IL-21能夠影響Treg？或常規(guī)T細胞,？或者是抗原呈遞細胞？目前還不明確,。
這里,，研究人員利用了來自IL-21R（IL-21受體）缺陷小鼠的淋巴細胞群，來準確確定IL-21靶向哪一種細胞類型,。他們發(fā)現(xiàn),，IL-21通過作用到常規(guī)T細胞，妨礙了Treg的抑制作用,。進一步研究發(fā)現(xiàn),，這與IL-21抑制IL-2的產(chǎn)生有關(guān)。
盡管沒有IL-2,，常規(guī)T細胞的免疫應(yīng)答能夠繼續(xù)進行,，這是因為IL-21能夠代替IL-2來作為T細胞的生長因子。然而,，IL-21不能夠代替IL-2來促進調(diào)節(jié)性T細胞的分隔,。因此，常規(guī)T細胞的IL-21通過減少IL-2的可用性，間接的影響了Treg的體內(nèi)平衡,。
該研究表明,，在促進常規(guī)T細胞應(yīng)答方面，IL-21與IL-2具有相同的作用,。但是,，在控制Treg的體內(nèi)平衡及功能方面，它們又彼此不同,。
該研究同時也表明了一個新的觀點,，即細胞因子能夠抑制IL-2，來促進機體的免疫力,。（生物谷Deepblue編譯）
doi: 10.1182/blood-2011-10-388546
PMC:
PMID:
IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
Kesley Attridge, Chun Jing Wang, Lukasz Wardzinski, Rupert Kenefeck, Jayne L. Chamberlain, Claire Manzotti, Manfred Kopf, and Lucy S. K. Walker.
Modulation of regulatory T cell (Treg) suppression has important implications for vaccine development, the effectiveness of tumor surveillance, and the emergence of autoimmunity.We have previously shown that the cytokine IL-21 can counteract Treg suppression. However, whether this reflects an effect of IL-21 on Treg, conventional T cells, or antigen-presenting cells is not known.Here we have used lymphocyte populations from IL-21R–deficient mice to pinpoint which cell type needs to be targeted by IL-21 for Treg suppression to be overcome.We show that IL-21 counteracts suppression by acting on conventional T cells and that this is associated with inhibition of IL-2 production. Despite the lack of IL-2, conventional T-cell responses proceed unimpaired because IL-21 can substitute for IL-2 as a T cell growth factor.However, IL-21 is unable to substitute for IL-2 in supporting the Treg compartment. Thus, IL-21 signaling in conventional T cells indirectly impacts Treg homeostasis by decreasing IL-2 availability.These data demonstrate that IL-21 and IL-2 can have overlapping roles in promoting conventional T-cell responses but play distinct roles in controlling Treg homeostasis and function. The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2
