title: Negligible immunogenicity of induced pluripotent stem cells derived from human skin fibroblasts.
abstract: Human induced pluripotent stem cells (hiPSCs) have potential applications in cell replacement therapy and regenerative medicine. However, limited information is available regarding the immunologic features of iPSCs. In this study, expression of MHC and T cell co-stimulatory molecules in hiPSCs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral blood mononuclear cells were examined. We found that no-integrate hiPSCs had no MHC-II and T cell co-stimulatory molecules expressions but had moderate level of MHC-I and HLA-G expressions. In contrast to human skin fibroblasts (HSFs) which significantly induced allogeneic T cell activation and proliferation, hiPSCs failed to induce allogeneic CD45+ lymphocyte and CD8+ T cell activation and proliferation but could induce a low level of allogeneic CD4+ T cell proliferation. Unlike HSFs which induced allogeneic lymphocytes to produce high levels of IFN-γ, TNF-α and IL-17, hiPSCs only induced allogeneic lymphocytes to produce IL-2 and IL-10, and promote IL-10-secreting regulatory T cell (Treg) generation. Our study suggests that the integration-free hiPSCs had low or negligible immunogenicity, which may result from their induction of IL-10-secreting Treg.
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Pediatrics, University Hospital of Hubei University for Nationalities, Enshi, Hubei, 445000, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Lu
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Meixing
authors.initials: M
authors.lastname: Yu
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Shen
authors.affiliation: Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Feng
authors.affiliation: Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Disease, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Li
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: The Joint Research Center of West China Second University Hospital of Sichuan University and Faculty of Medicine of the University of Hong Kong, Sichuan University, Chengdu, Sichuan, 610041, China; Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation / Q000235:genetics; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: C508609:IL10 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D007376:Interleukin-2; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma