
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.
CD4-Positive T-Lymphocytes, Mice, Knockout, CD3 Complex, Cell Culture Techniques, Receptors, Antigen, T-Cell, Mice, Transgenic, Lymphocyte Activation, Transcription Factor AP-1, Mice, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Animals, Interleukin-2, Calcium, Lymph Nodes, Phosphorylation, Spleen, Adaptor Proteins, Signal Transducing
CD4-Positive T-Lymphocytes, Mice, Knockout, CD3 Complex, Cell Culture Techniques, Receptors, Antigen, T-Cell, Mice, Transgenic, Lymphocyte Activation, Transcription Factor AP-1, Mice, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Animals, Interleukin-2, Calcium, Lymph Nodes, Phosphorylation, Spleen, Adaptor Proteins, Signal Transducing
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