Lck activity controls CD4/CD8 T cell lineage commitment

Immunity. 2000 Mar;12(3):313-22. doi: 10.1016/s1074-7613(00)80184-3.


Thymocytes carrying MHC class I-restricted TCRs differentiate into CD8 T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class II-restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I-restricted TCR develop into functional CD4 T cells when Lck activity is increased. These results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Ligand
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Lineage / physiology*
  • Female
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Leukopoiesis / physiology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology*
  • Male
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic
  • Thymus Gland / cytology
  • Up-Regulation / immunology


  • CD28 Antigens
  • CD3 Complex
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • CD40 Ligand
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)