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.
Antigen-specific T cells derived from human iPS cells In vitro thymopoiesis Re-differentiation of antigen-specific T cells T cell receptor rearrangement T cell immunotherapy
This is a preview of subscription content, log in to check access.
Springer Nature is developing a new tool to find and evaluate Protocols. Learn more
Rosenberg SA, Restifo NP, Yang JC et al (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 84:299–308CrossRefGoogle Scholar
Nishimura T, Kaneko S, Kawana-Tachikawa A et al (2013) Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell 12(1):114–126CrossRefPubMedGoogle Scholar
Vizcardo R, Masuda K, Yamada D et al (2013) Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell 12(1):31–36CrossRefPubMedGoogle Scholar
Takayama N, Eto K (2012) In vitro generation of megakaryocytes and platelets from human embryonic stem cells and induced pluripotent stem cells. Methods Mol Biol 788:205–217CrossRefPubMedGoogle Scholar
Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872CrossRefPubMedGoogle Scholar
Nishimura K, Sano M, Ohtaka M et al (2011) Development of defective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J Biol Chem 286:4760–4771CrossRefPubMedGoogle Scholar