Lck和Fyn蛋白酪氨酸激酶对上皮内淋巴细胞发育的不同贡献。

Differential contribution of Lck and Fyn protein tyrosine kinases to intraepithelial lymphocyte development.

作者信息

Page S T, van Oers N S, Perlmutter R M, Weiss A, Pullen A M

机构信息

Department of Immunology, University of Washington, Seattle 98195-7370, USA.

出版信息

Eur J Immunol. 1997 Feb;27(2):554-62. doi: 10.1002/eji.1830270229.

DOI:10.1002/eji.1830270229

PMID:9045930

Abstract

The developmental stages and the role of protein tyrosine kinases (PTK) in the maturation of CD3+CD8 alpha alpha+ intraepithelial lymphocytes (IEL) have not been extensively characterized. However, comparisons of thymic and extrathymic T cell development indicate that these processes involve some distinct signaling and selection events. We used mice deficient in Lck, Fyn, or both Lck and Fyn to analyze the role that these src-family PTK play in IEL development. In contrast to thymocyte development, we found that all IEL subsets develop in mice deficient for either kinase alone. However, lck-/- animals exhibited reduced numbers of TcR alphabeta+ CD8alpha alpha+ IEL, indicating that Lck is important in the development of these cells. Mice which lack both Lck and Fyn fail to generate TcR alphabeta+ IEL, suggesting that signaling through the preTcR, mediated by Lck and, to a lesser extent Fyn, is required for maturation of all TcR alphabeta+ IEL lineages. Interestingly, a small population of TcR gammadelta+ CD8 alpha alpha+ cells are apparent in lck-/-fyn-/- animals, demonstrating that TcR alphabeta+ CD8 alpha alpha+ and TcR gammadelta+ CD8alpha alpha+ IEL have distinct PTK requirements for their development or expansion. CD3-CD8alpha- CD44+ and CD3-CD8alpha alpha+ CD16/32+ B220+ cells comprise the majority of IEL in both lck-/- fyn-/- and rag -/- mice, while they are poorly represented in wildtype controls. Comparison of the cell surface phenotype of these putative precursor IEL in lck-/- fyn-/- and rag-/- animals suggests that IEL maturation in these animals is arrested at an equivalent developmental stage. Overall, the data presented demonstrate that signals mediated by Lck or Fyn direct TcR alphabeta+ CD8alpha alpha+ IEL maturation but are dispensable for the development of TcR gammadelta+ CD8 alpha alpha+ IEL.

摘要

蛋白酪氨酸激酶（PTK）在CD3⁺CD8αα⁺上皮内淋巴细胞（IEL）成熟过程中的发育阶段及作用尚未得到广泛研究。然而，胸腺内和胸腺外T细胞发育的比较表明，这些过程涉及一些不同的信号传导和选择事件。我们利用缺乏Lck、Fyn或同时缺乏Lck和Fyn的小鼠来分析这些src家族PTK在IEL发育中的作用。与胸腺细胞发育不同，我们发现单独缺乏任何一种激酶的小鼠中所有IEL亚群均能发育。然而，lck⁻/⁻动物的TcRαβ⁺CD8αα⁺IEL数量减少，表明Lck对这些细胞的发育很重要。同时缺乏Lck和Fyn的小鼠无法产生TcRαβ⁺IEL，这表明由Lck介导且在较小程度上由Fyn介导的通过前体TcR的信号传导是所有TcRαβ⁺IEL谱系成熟所必需的。有趣的是，在lck⁻/⁻fyn⁻/⁻动物中可明显看到一小群TcRγδ⁺CD8αα⁺细胞，这表明TcRαβ⁺CD8αα⁺和TcRγδ⁺CD8αα⁺IEL在发育或扩增过程中有不同的PTK需求。CD3⁻CD8α⁻CD44⁺和CD3⁻CD8αα⁺CD16/32⁺B220⁺细胞在lck⁻/⁻fyn⁻/⁻和rag⁻/⁻小鼠中占IEL的大多数，而在野生型对照中则占比很少。对lck⁻/⁻fyn⁻/⁻和rag⁻/⁻动物中这些假定的前体IEL细胞表面表型的比较表明，这些动物中的IEL成熟在相同的发育阶段停滞。总体而言，所呈现的数据表明，由Lck或Fyn介导的信号指导TcRαβ⁺CD8αα⁺IEL成熟，但对TcRγδ⁺CD8αα⁺IEL的发育并非必需。