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

Life Sci Alliance. 2020 Jan 24;3(2):e202000642. doi: 10.26508/lsa.202000642. Print 2020 Feb.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / genetics*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Immunity, Innate*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / genetics
  • Thymocytes / immunology
  • Transfection


  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Cd8b1 protein, mouse
  • Receptors, Antigen, T-Cell