title: Interleukin-2 Enhances the Regulatory Functions of CD4(+)T Cell-Derived CD4(-)CD8(-) Double Negative T Cells.
abstract: CD4(+) T cells can be converted to CD4(-)CD8(-) double negative T cells (DN T cells) under appropriate conditions, and IL-2 enhanced the conversion. Here, we investigated the effect of IL-2 on the proliferation and function of converted DN T cells in vitro and in vivo. DN T cells were hyporesponsive when restimulated by mature dendritic cells (mDCs), IL-2 completely restored their responsiveness in vitro. In addition, IL-2 increased the resistance of DN T cells to apoptosis in vivo. DN T cells profoundly inhibited the proliferation of CD4(+)CD25(-) T effector cells triggered by mDCs in vitro, and this suppression was further enhanced by IL-2. Adoptively transferring of DN T cells, in combination with IL-2, inhibited the proliferation and enhanced apoptosis of alloreactive CD4(+) T cells, which resulted in significant prolongation of skin allograft survival time. Perforin plays a key role in the enhancement of DN T cells immune regulation by IL-2. In conclusion, we elucidated that IL-2 promoted DN T cell proliferation and suppressive function. The combination of DN T cells and exogenous IL-2 may represent a novel therapy in the clinical setting to prevent allograft rejection and induce immune tolerance.
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Min
authors.initials: M
authors.lastname: Cong
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Tianhui
authors.initials: T
authors.lastname: Liu
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Dan
authors.initials: D
authors.lastname: Tian
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: 3 National Clinical Research Center of Digestive Diseases , Beijing, China .
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Yue
authors.initials: Y
authors.lastname: Tian
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|3 National Clinical Research Center of Digestive Diseases , Beijing, China .
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.affiliation: 3 National Clinical Research Center of Digestive Diseases , Beijing, China .|4 Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis , Beijing, China .
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
authors.affiliation: 1 Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University , Beijing, China .|2 Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation , Beijing, China .|3 National Clinical Research Center of Digestive Diseases , Beijing, China .
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2