Lck和Fyn对T细胞发育过程的影响

胸腺中T细胞的发育及次级淋巴组织中成熟T细胞的活化均需要细胞能够对环境信号分子做出适应性的反应。在共刺激分子及细胞因子受体介导的信号参与下通过TCR(T cell receptor)及其辅助受体CD4和CD8与MHC/抗原肽复合物相互作用,可以诱导TCR信号通路激活并最终导致T细胞免疫反应的发生。Src家族激酶Lck(Lymphocyte-specific protein tyrosine kinase)和Fyn(Proto-oncogene tyrosine-protein kinase)的激活是启动TCR信号通路的关键因素。在T细胞的发育、阳性选择、初始T细胞的外周存活及由淋巴细胞缺失诱导的细胞增殖中都起着关键性的作用。研究显示,虽然这两种信号分子紧密相关,但在某些条件下Lck发挥着比Fyn更重要的作用,并且Fyn仅可以补充Lck的部分功能。文章针对这两个激酶在T细胞发育的整个过程中的作用机制进行了论述。

Function of the Lck and Fyn in T cell development

The development of T cell in the thymus and the activation of mature T cells in the secondary lymphoid tissues require T cell to make adaptive responses to signaling molecules of environment. The activation of T cell receptor (TCR) signaling pathway could be induced by the interaction of the TCR and its co-receptor CD4 and CD8 with MHC/peptide complex. This process involves co-stimulatory molecules and signals mediated by cytokine receptors, which eventually leads to the occurrence of T cell immune response. The Src-family kinases lymphocyte-specific protein tyrosine kinase (Lck) and proto-oncogene tyrosine-protein kinase (Fyn) are expressed in T cells and serve as the signaling molecules that are activated downstream of TCR. These signaling molecules play key roles in development, positive selection, and peripheral maintenance of naive T cells and lymphopenia-induced proliferation of peripheral T cells. Both Lck and Fyn are required for each of these TCR-based signaling pathways, and Lck seems to be the major contributor, while Fyn can only supplement some functions of Lck. In this review, we discussed the mechanisms by which these two proteins perform functions in T cell development based on our current understanding.