Pa. Trobridge et al., Positive and negative selection of thymocytes depends on Lck interaction with the CD4 and CD8 coreceptors, J IMMUNOL, 166(2), 2001, pp. 809-818
Considerable evidence supports a role for the Src family protein tyrosine k
inase Lck in regulating multiple aspects of thymocyte development. In this
report, we establish that early events in T lymphopoiesis are restored to L
ck-deficient mice by provision of a transgene encoding a version of Lck tha
t cannot interact with the coreceptors CD4 and CD8. In addition, we demonst
rate that later events in thymocyte development, specifically, the processe
s of positive and negative selection, are compromised in mire where the onl
y Lck available cannot associate with either CD4 or CD8. We conclude that n
ot only is Lck activity required for positive and negative selection, but t
hat that activity must be coupled to the CD4 and CD8 coreceptors.