title: IL-15 and dendritic cells induce proliferation of CD4+CD25+ regulatory T cells from peripheral blood.
abstract: 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.
authors: Department of Nephrology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Shuxiong
authors: S
authors: Xu
authors: Zhaolin
authors: Z
authors: Sun
authors: Yan
authors: Y
authors: Sun
authors: Jianguo
authors: J
authors: Zhu
authors: Xiaowei
authors: X
authors: Li
authors: Xinqi
authors: X
authors: Zhang
authors: Gang
authors: G
authors: Shan
authors: Zhenxing
authors: Z
authors: Wang
authors: Hong
authors: H
authors: Liu
authors: Xiongfei
authors: X
authors: Wu
mesh_terms: D015704:CD4 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D015704:CD4 Antigens; C436291:CDKN1B protein, human; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D050791:STAT Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27