Activation of naïve CD4 T cells by anti-CD3 reveals an important role for Fyn in Lck-mediated signaling.
Proc Natl Acad Sci U S A
; 101(41): 14859-64, 2004 Oct 12.
Article
em En
| MEDLINE
| ID: mdl-15465914
ABSTRACT
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-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 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Complexo CD3
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Proteína Tirosina Quinase p56(lck) Linfócito-Específica
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Proteínas Adaptadoras de Transdução de Sinal
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos