title: In Vitro Generation of Antigen-Specific T Cells from Induced Pluripotent Stem Cells of Antigen-Specific T Cell Origin.
abstract: Induced pluripotent stem (iPS) cells derived from T lymphocyte (T-iPS cells) preserve the T cell receptor (TCR) α and β gene rearrangements identical to the original T cell clone. Re-differentiated CD8 single positive αβ T cells from the T-iPS cells exhibited antigen-specific cytotoxicity, improved proliferative response, and elongation of telomere indicating rejuvenation of antigen specific T cell immunity in vitro. To regenerate antigen specific cytotoxic T lymphocytes (CTL), first, we have optimized a method for reprogramming-resistant CD8 T cell clones into T-iPS cells by using sendaiviral vectors. Second, we have optimized stepwise differentiation methods for inducing hematopoietic progenitor cells, T cell progenitors, and functionally matured CD8 single positive CTL. These protocols provide useful in vitro tools and models both for research of antigen-specific T cell immunotherapy and for research of normal and pathological thymopoiesis.
authors.affiliation: Laboratory of Regenerative Immunotherapy, Department of Cell Growth and Differentiation, Center for iPS cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin Yoshida, Sakyo-ku, Kyoto, Shogoin, 606-8507, Japan. kaneko.shin@cira.kyoto-u.ac.jp.
authors.forename: Shin
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D003602:Cytotoxicity, Immunologic; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Antigen-specific T cells derived from human iPS cells; In vitro thymopoiesis; Re-differentiation of antigen-specific T cells; T cell immunotherapy; T cell receptor rearrangement