Normal development and activation but altered cytokine production of Fyn-deficient CD4+ T cells.
Normal development and activation but altered cytokine production of Fyn-deficient CD4+ T cells.
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正常发育和激活，但改变了缺乏Fyn的CD4+ T细胞的细胞因子产生。
DOI：
10.4049/jimmunol.181.8.5374
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发表时间：
2008-10-15
期刊：
影响因子：
--
通讯作者：
DeFranco AL
中科院分区：
文献类型：
--
作者：
Mamchak AA;Sullivan BM;Hou B;Lee LM;Gilden JK;Krummel MF;Locksley RM;DeFranco AL
Src家族激酶Fyn在T细胞中表达，并被证明能够磷酸化参与TCR信号传导、细胞骨架重组和IL-4产生的蛋白。fyn缺陷小鼠的NKT细胞数量大大减少，胸腺细胞和T细胞在其tcr抗体交联后反应受损。在这里，我们研究了Fyn在肽/MHC ii类诱导的CD4+ T细胞反应中的作用。在fynn缺陷小鼠中，表达DO11.10 TCR转基因的CD4+ T细胞发育正常，外周血中naïve和调节性DO11.10+CD4+ T细胞的数量和表型与野生型相当。与装载Ovap323-339的apc结合，以及随后的DO11.10+ fyn缺陷CD4+ T细胞在体外或体内的增殖，与DO11.10+野生型CD4+ T细胞的反应几乎没有区别。fyn缺陷T细胞的增殖不依赖于CD28的共刺激。此外，我们发现，无论在体外还是体内，转基因CD4+ fyn缺陷T细胞向IL-4分泌效应细胞的分化均未受到损害，并且在一定条件下，DO11.10+ fyn缺陷CD4+ T细胞比DO11.10+野生型CD4+ T细胞更能产生细胞因子。这些数据表明，Fyn表达的减少不会改变大多数抗原驱动的CD4+ T细胞反应，除了细胞因子的产生，在某些情况下，Fyn缺乏的CD4+ T细胞会增强细胞因子的产生。
The Src family kinase, Fyn, is expressed in T cells and has been shown to phosphorylate proteins involved in TCR signaling, cytoskeletal reorganization and IL-4 production. Fyn-deficient mice have greatly decreased numbers of NKT cells, and have thymocytes and T cells with compromised responses following antibody cross-linking of their TCRs. Here we have addressed the role of Fyn in peptide/MHC class II-induced CD4+ T cell responses. In Fyn-deficient mice, CD4+ T cells expressing the DO11.10 TCR transgene developed normally, and the number and phenotype of naïve and regulatory DO11.10+CD4+ T cells in the periphery were comparable with their wild type counterparts. Conjugation with Ovap323-339 loaded APCs, and the subsequent proliferation in vitro or in vivo of DO11.10+Fyn-deficient CD4+ T cells was virtually indistinguishable from the response of DO11.10+ wild type CD4+ T cells. Proliferation of Fyn-deficient T cells was not more dependent on co-stimulation through CD28. In addition, we have found that differentiation, in vitro or in vivo, of transgenic CD4+ Fyn-deficient T cells into IL-4 secreting effector cells was unimpaired, and under certain conditions DO11.10+Fyn-deficient CD4+ T cells were more potent cytokine-producing cells than DO11.10+ wild type CD4+ T cells. These data demonstrate that ablation of Fyn expression does not alter most antigen-driven CD4+ T cell responses with the exception of cytokine production, which under some circumstances, is enhanced in Fyn-deficient CD4+ T cells.
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影响因子：
4.4
作者：
Martin-Cofreces, Noa B.;Sancho, David;Sanchez-Madrid, Francisco
通讯作者：
Sanchez-Madrid, Francisco
DOI：
10.1084/jem.20030976
发表时间：
2004-01-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Badour K;Zhang J;Shi F;Leng Y;Collins M;Siminovitch KA
通讯作者：
Siminovitch KA
影响因子：
5.3
作者：
GAUEN, LKT;ZHU, YX;SHAW, AS
通讯作者：
SHAW, AS
DOI：
10.1165/ajrcmb.24.4.4266
发表时间：
2001-04-01
影响因子：
6.4
作者：
Kudlacz, EM;Andresen, CJ;Changelian, PS
通讯作者：
Changelian, PS
影响因子：
32.4
作者：
Grogan, JL;Mohrs, M;Locksley, RM
通讯作者：
Locksley, RM