TY - JOUR
T1 - Activation of naïve CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling
AU - Sugie, Katsuji
AU - Jeon, Myung Shin
AU - Grey, Howard M.
PY - 2004/10/12
Y1 - 2004/10/12
N2 - Although there was no impairment in IL-2 secretion and proliferation of Fyn-deficient naïve 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 naïve CD4 cells with anti-CD3 activated Lck and initiated the signaling cascade downstream of Lck, including phosphorylation of ZAP-70, LAT, and PLC-γ1; 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 naïve 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 naïve T cells is restricted to the T cell antigen receptor, Fyn plays an essential role by positive regulation of Lck activity.
AB - Although there was no impairment in IL-2 secretion and proliferation of Fyn-deficient naïve 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 naïve CD4 cells with anti-CD3 activated Lck and initiated the signaling cascade downstream of Lck, including phosphorylation of ZAP-70, LAT, and PLC-γ1; 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 naïve 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 naïve T cells is restricted to the T cell antigen receptor, Fyn plays an essential role by positive regulation of Lck activity.
UR - http://www.scopus.com/inward/record.url?scp=6944241415&partnerID=8YFLogxK
U2 - 10.1073/pnas.0406168101
DO - 10.1073/pnas.0406168101
M3 - Article
C2 - 15465914
AN - SCOPUS:6944241415
SN - 0027-8424
VL - 101
SP - 14859
EP - 14864
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -