2026-01-09 カナダ・ブリティッシュコロンビア大学(UBC)
<関連情報>
- https://news.ubc.ca/2026/01/stem-cell-engineering-helper-t-cells/
- https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(25)00444-8
多能性幹細胞からのヒトCD4+ およびCD8+ T細胞の調整可能な分化 Tunable differentiation of human CD4+ and CD8+ T cells from pluripotent stem cells
Ross D. Jones ∙ Kevin Salim ∙ Laura N. Stankiewicz ∙ … ∙ Fabio M.V. Rossi ∙ Megan K. Levings ∙ Peter W. Zandstra
Cell Stem Cell Published:January 08, 2026
DOI:https://doi.org/10.1016/j.stem.2025.12.010
Graphical abstract
Highlights
- Notch suppresses in vitro production of CD4+ T cells from PSCs
- Notch represses TCR signaling outputs, including the CD4 lineage factor ThPOK
- PSC-CD4+ T cells express naive/memory T cell markers and diverse TCRs
- PSC-CD4+ T cells express co-stimulatory receptors and can polarize in vitro
Summary
Allogeneic T cell therapies are a highly desirable option to circumvent the cost and complexity of using autologous T cells to treat diseases. Allogeneic CD8+ T cells can be made from pluripotent stem cells (PSCs), but deriving CD4+ T cells from PSCs has remained a significant challenge. Using feeder- and serum-free conditions, we found that CD4+ vs. CD8+ T cell commitment from PSCs can be controlled by fine-tuning the dynamics of Notch and T cell receptor (TCR) signaling delivered to CD4+CD8+ double-positive T cells. Notch signaling negatively impacts CD4+ T cell commitment, and its timed removal allows generation of clonally diverse and expandable CD4+ T cells from PSCs. The resulting CD4+ T cells respond to cytokine-mediated polarization by differentiating into Th1, Th2, or Th17 cells, recapitulating canonical helper cell function. These findings represent a significant step toward using PSC-derived CD4+ T cells as a low-cost, off-the-shelf cell therapy.
