Constitutive CD8 expression drives innate CD8+ T-cell differentiation via induction of iNKT2 cells

Satoshi Kojo, Michiko Ohno-Oishi, Hisashi Wada, Sebastian Nieke, Wooseok Seo, Sawako Muroi, Ichiro Taniuchi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Temporal down-regulation of the CD8 co-receptor after receiving positive-selection signals has been proposed to serve as an important determinant to segregate helper versus cytotoxic lineages by generating differences in the duration of TCR signaling between MHC-I and MHC-II selected thymocytes. By contrast, little is known about whether CD8 also modulates TCR signaling engaged by the non-classical MHC-I–like molecule, CD1d, during development of invariant natural killer T (iNKT) cells. Here, we show that constitutive transgenic CD8 expression resulted in enhanced differentiation of innate memory-like CD8+ thymocytes in both a cell-intrinsic and cell-extrinsic manner, the latter being accomplished by an increase in the IL-4–producing iNKT2 subset. Skewed iNKT2 differentiation requires cysteine residues in the intracellular domain of CD8α that are essential for transmitting cellular signaling. Collectively, these findings shed a new light on the relevance of CD8 down-regulation in shaping the balance of iNKT-cell subsets by modulating TCR signaling.

Original languageEnglish
Article numbere202000642
JournalLife Science Alliance
Issue number2
Publication statusPublished - 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis


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