Filby Andrew, Seddon Benedict, Kleczkowska Joanna, Salmond Robert, Tomlinson Peter, Smida Michal, Lindquist Jonathan A, Schraven Burkhart, Zamoyska Rose
Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, The Ridgeway, London, United Kingdom.
J Immunol. 2007 Oct 1;179(7):4635-44. doi: 10.4049/jimmunol.179.7.4635.
In naive T cells, engagement of the TCR with agonist peptide:MHC molecules leads to phosphorylation of key intracellular signaling intermediates within seconds and this peaks within minutes. However, the cell does not commit to proliferation and IL-2 cytokine production unless receptor contact is sustained for several hours. The biochemical basis for this transition to full activation may underlie how T cells receive survival signals while maintaining tolerance, and is currently not well understood. We show here that for CD8 T cells commitment to proliferation and cytokine production requires sustained activation of the Src family kinase Lck and is opposed by the action of Fyn. Thus, in the absence of Fyn, commitment to activation occurs more rapidly, the cells produce more IL-2, and undergo more rounds of division. Our data demonstrate a role for Fyn in modulating the response to Ag in primary T cells.
在初始T细胞中，TCR与激动剂肽：MHC分子的结合会在数秒内导致关键细胞内信号转导中间体的磷酸化，且在数分钟内达到峰值。然而，除非受体接触持续数小时，细胞不会进入增殖和白细胞介素-2细胞因子产生阶段。这种向完全激活转变的生化基础可能是T细胞在维持耐受性的同时如何接收存活信号的基础，目前对此还了解甚少。我们在此表明，对于CD8 T细胞而言，进入增殖和细胞因子产生阶段需要Src家族激酶Lck的持续激活，并且受到Fyn作用的抑制。因此，在没有Fyn的情况下，进入激活阶段的速度更快，细胞产生更多的白细胞介素-2，并经历更多轮的分裂。我们的数据证明了Fyn在调节原代T细胞对抗原的反应中的作用。
