Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk

Immunity. 2006 Jul;25(1):93-104. doi: 10.1016/j.immuni.2006.05.011.

Abstract

Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca(2+) mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk(-/-) and Rlk(-/-)Itk(-/-) mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8(+) T cells in these mice do not resemble conventional CD8(+) T cells. Instead, these cells express memory markers, rapidly produce interferon-gamma, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted "innate-type" lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8(+) T cell phenotypes in Itk(-/-) mice, arguing that altered signaling permits development of this innate-type CD8(+) cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation*
  • Cell Lineage*
  • Histocompatibility Antigens / metabolism
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Phenotype
  • Protein-Tyrosine Kinases / classification
  • Protein-Tyrosine Kinases / deficiency*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Time Factors

Substances

  • Histocompatibility Antigens
  • Tec protein-tyrosine kinase
  • Protein-Tyrosine Kinases
  • emt protein-tyrosine kinase