期刊
IMMUNOLOGY LETTERS
卷 140, 期 1-2, 页码 59-67出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2011.06.005
关键词
Dendritic cells; IL-15; Regulatory T cells; Proliferation
类别
资金
- National Natural Science Foundation of China [30772048]
- Natural Science Foundation of Chongqing [CSTC 2006BB5066]
- Clinical Innovative Foundation of Southwest Hospital [SWH2006A003]
- Governor's Foundation for Excellent Talents of Science and Technology in Guizhou Province [(2005)230, (2009)31]
- Foundation of Guizhou Provincial Science and Technology Department [(2009)2221, (2011)2249]
CD4(+)CD25(+) regulatory T cells (Tregs) have recently been the subject of intense research due to their strong immunosuppressive effect. Increasing evidence suggests that IL-15 plays an important role in Tregs biology. Nevertheless, the mechanism by which IL-15 performs this function remains to be fully elucidated. To address this question, we isolated Tregs from human peripheral blood, and utilized IL-15, dendritic cells (DCs), or DCs combined with IL-15, to examine the proliferation of Tregs and to explore related molecular mechanisms. Here, we show that IL-15 can induce the proliferation of Tregs in the presence of DCs. The induction is mediated by DCs presenting IL-15 in trans to Tregs. Simultaneously, DCs-derived IL-2, regulated by IL-15, may also play a supportive role. After IL-15 withdrawal, IL-15 trans-endosomal recycling in DCs contributes to the proliferation of Tregs. The activation of Akt, Erk1/2 and STAT(5), and the degradation of p27(kip1) may be involved in this process. These findings might explain the proliferation of Tregs in the absence of IL-2 in vivo and provide a novel method to achieve large-scale proliferation of Tregs in vitro in order to obtain cell numbers sufficient for immunotherapy. (C) 2011 Published by Elsevier B.V.
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