Requirements for selection of conventional and innate T lymphocyte lineages

Immunity. 2007 Nov;27(5):775-85. doi: 10.1016/j.immuni.2007.09.012.


Mice deficient in the Tec kinase Itk develop a large population of CD8(+) T cells with properties, including expression of memory markers, rapid production of cytokines, and dependence on Interleukin-15, resembling NKT and other innate T cell lineages. Like NKT cells, these CD8(+) T cells can be selected on hematopoietic cells. We demonstrate that these CD8(+) T cell phenotypes resulted from selection on hematopoietic cells-forcing selection on the thymic stroma reduced the number and innate phenotypes of mature Itk-deficient CD8(+) T cells. We further show that, similar to NKT cells, selection of innate-type CD8(+) T cells in Itk(-/-) mice required the adaptor SAP. Acquisition of their innate characteristics, however, required CD28. Our results suggest that SAP and Itk reciprocally regulate selection of innate and conventional CD8(+) T cells on hematopoietic cells and thymic epithelium, respectively, whereas CD28 regulates development of innate phenotypes resulting from selection on hematopoietic cells.

MeSH terms

  • Animals
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology*
  • Flow Cytometry
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Precursor Cells, T-Lymphoid / cytology*
  • Precursor Cells, T-Lymphoid / immunology
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology


  • CD28 Antigens
  • Intracellular Signaling Peptides and Proteins
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Ltk protein, mouse
  • Receptor Protein-Tyrosine Kinases