alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases

Immunity. 1996 Nov;5(5):429-36. doi: 10.1016/s1074-7613(00)80499-9.


Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show that the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completely arrests alpha beta T cell development at the CD4-CD8- stage. The development of V gamma 3+ dendritic epidermal T cells is also severely impaired, but natural killer cell development and cytolytic activity is unaffected in lck(-/-)fyn(-/-) mice. These findings reveal the potential for redundant functions mediated by Src family PTKs while emphasizing crucial roles for Lck and Fyn in T cell development.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Lymphocyte Activation / genetics
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Protein-Tyrosine Kinases / deficiency
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocyte Subsets / immunology*
  • src-Family Kinases / deficiency*


  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases