Redifferentiation of Adaptive Naïve-Like CTL from T-Cell-Derived iPSC

Methods Mol Biol. 2019:2048:71-75. doi: 10.1007/978-1-4939-9728-2_7.

Abstract

In this chapter, we describe redifferentiation procedures from iPSCs to CD8αβ+ cytotoxic T cells in 10 T1/2 and OP9/DL1 feeder condition. iPSC used here is derived from T-cell clone (T-iPSC), which has lost naïve phenotype and acquired exhaustion/senescence phenotype during cloning process (Note 1). On the other hand, redifferentiated T cells (T-iPSC-Ts) reacquire naïve phenotype (CD45RA+CD45RO-CCR7+CD62L+), which are reportedly critical for in vivo persistence of infused T cells and greatly affect therapeutic efficacy of adoptive immunotherapy. Indeed, T-iPSC-Ts exhibit much superior proliferative capacity while retaining equivalent effector function compared to parental T-cell clones. Here, we demonstrate the methodology to produce naïve-like T-iPSC-Ts, which could be potent cell source for adoptive immunotherapy.

Keywords: Adaptive; CCR7; CTL; Naïve; Nkp44; iPSC.

MeSH terms

  • Animals
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cell Differentiation
  • Cell Line
  • Coculture Techniques / instrumentation
  • Coculture Techniques / methods
  • Humans
  • Immunologic Memory
  • Immunotherapy, Adoptive / methods
  • Induced Pluripotent Stem Cells
  • Mesenchymal Stem Cells
  • Mice
  • T-Lymphocytes, Cytotoxic / physiology*
  • T-Lymphocytes, Cytotoxic / transplantation