SAP protein-dependent natural killer T-like cells regulate the development of CD8(+) T cells with innate lymphocyte characteristics

Immunity. 2010 Aug 27;33(2):203-15. doi: 10.1016/j.immuni.2010.07.013. Epub 2010 Jul 30.


CD8(+) T cells are selected via low-affinity interaction with MHC class I molecules on thymic epithelial cells (TECs). However, compromised T cell receptor signaling was proposed to force CD8(+) T cell selection on hematopoietic cells through a SLAM-associated protein (SAP)-dependent mechanism similar to NKT cells. The outcome is an unconventional CD8(+) T cell with phenotypic and functional characteristics of innate lymphocytes. Here we showed that Id3(-/-) CD8(+) T cells had an innate-like phenotype and required SAP for their development. However, like conventional CD8(+) T cells, Id3(-/-) CD8(+) thymocytes were selected on TECs. The requirement for SAP and the innate-like phenotype was not intrinsic to Id3(-/-) CD8(+) thymocytes. Rather, an expanded population of NKT-like cells induced the innate phenotype on CD8(+) T cells through production of interleukin-4. Our findings reveal that accumulation of NKT-like cells promotes conventional CD8(+) thymocytes to acquire innate lymphocyte characteristics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation*
  • Cells, Cultured
  • Histocompatibility Antigens Class I / immunology
  • Immunity, Innate*
  • Inhibitor of Differentiation Proteins / deficiency
  • Inhibitor of Differentiation Proteins / immunology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / immunology
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / immunology*
  • Phenotype
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Thymus Gland / cytology
  • Thymus Gland / immunology


  • Histocompatibility Antigens Class I
  • Inhibitor of Differentiation Proteins
  • Intracellular Signaling Peptides and Proteins
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Idb3 protein, mouse
  • Interleukin-4