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Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, United Kingdom
The role of TCR signals triggered by recognition of self MHCs in
maintaining the survival of naive peripheral T cells remains
controversial. Here we examine the role of the Src family kinases,
p56lck (Lck) and p59fyn
(Fyn), in the survival of naive T cells. We show that long term
survival requires a combination of signals transduced by Src family
kinases and signals through the IL-7R. In the absence of either one,
naive T cells die slowly, but if both signals are removed, cell loss is
greatly accelerated. The TCR signal can be mediated by either Fyn or
Lck at wild-type levels of expression, but not by Lck alone if
expressed suboptimally. The disappearance of T cells in the absence of
Fyn and Lck was associated with a complete loss of TCR
-chain
phosphorylation and down-regulation of CD5, both of which are also MHC
contact dependent, indicating that the Src family kinases are critical
for transducing a TCR-MHC survival signal.
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