TY - JOUR
T1 - αβ T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases
AU - Van Oers, Nicolai S C
AU - Lowin-Kropf, Bente
AU - Finlay, Deborah
AU - Connolly, Kari
AU - Weiss, Arthur
N1 - Funding Information:
Correspondence should be addressed to A. W. This work was supported in part by grants from the National Institutes of Health (GM-39553 to A. W.), the Human Frontier Science Program Organization (LT-505/93 to N. S. C. v. O.), the Boehringer Ingelheim Fonds (B. L.-K.), and the Scleroderma Research Foundation (K. C.). We would like to thank Drs. Roger Perlmutter and Tak Mak for providing the fyn and lck null mice, respectively. We would like to thank Drs. Nigel Killeen, Virginia Smith-Shapiro, and Dapeng Qian and David Chu and Jun Wu for their critical reading of the manuscript and helpful suggestions. We would also like to thank Dr. Cynthia Guidos and colleagues (Hospital for Sick Children, Toronto, Canada) for sharing data on their lck and lck / fyn knockout mice prior to publication.
PY - 1996/11
Y1 - 1996/11
N2 - 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 αβ T cell development at the CD4-CD8- stage. The development of Vγ3+ 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.
AB - 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 αβ T cell development at the CD4-CD8- stage. The development of Vγ3+ 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.
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U2 - 10.1016/S1074-7613(00)80499-9
DO - 10.1016/S1074-7613(00)80499-9
M3 - Article
C2 - 8934570
AN - SCOPUS:0030293791
SN - 1074-7613
VL - 5
SP - 429
EP - 436
JO - Immunity
JF - Immunity
IS - 5
ER -