alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases.
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.
van Oers
N S
NS
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Lowin-Kropf
B
B
Finlay
D
D
Connolly
K
K
Weiss
A
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D011518:Proto-Oncogene Proteins / Q000172:deficiency*; D051076:Proto-Oncogene Proteins c-fyn; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019061:src-Family Kinases / Q000172:deficiency*
D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases