Activation of naive CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling

作者：Sugie K; Jeon MS; Grey HM^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(41): 14859-14864.

DOI：10.1073/pnas.0406168101

Although there was no impairment in IL-2 secretion and proliferation of Fyn-deficient naive CD4 cells after stimulation with antigen and antigen-presenting cells, stimulation of these cells with anti-CD3 and anti-CD28 revealed profound defects. Crosslinking of purified wild-type naive CD4 cells with anti-CD3 activated Lck and initiated the signaling cascade downstream of Lck, including phosphorylation of ZAP-70, LAT, and PLC-gamma1; calcium flux; and dephosphorylation and nuclear translocation of the nuclear factor of activated T cells (NFAT)p. All of these signaling events were diminished severely in Fyn-deficient naive cells activated by CD3 crosslinking. Coaggregation of CD3 and CD4 reconstituted this Lck-dependent signaling pathway in Fyn(-/-) T cells. These results suggest that when signaling of naive T cells is restricted to the T cell antigen receptor, Fyn plays an essential role by positive regulation of Lck activity.

• 出版日期2004-10-12