Co-engagement of α4β1 integrin (VLA-4) and CD4 or CD8 is necessary to induce maximal Erk1/2 phosphorylation and cytokine production in human T cells
Co-engagement of α4β1 integrin (VLA-4) and CD4 or CD8 is necessary to induce maximal Erk1/2 phosphorylation and cytokine production in human T cells
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DOI：
10.1016/j.humimm.2009.09.360
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发表时间：
2010-01-01
期刊：
影响因子：
2.7
通讯作者：
Komanduri, Krishna V.
中科院分区：
文献类型：
--
作者：
Kim, Tae Kon;Billard, Matthew J.;Komanduri, Krishna V.
α (4) β(1)整合素VLA-4（极晚活化抗原4）和谱系特异性CD4和CD8受体被认为是T细胞上可能的共刺激受体。为了评估信号通过TCR、CD28和这些辅助分子的相对贡献，我们使用识别所有四种T细胞受体（CD3、CD28、CD4/CD8和VLA-4）的可溶性抗体激活人类T细胞，并使用高阶流式细胞术检测细胞内Erk1/2磷酸化和IL-2和ifn - γ的产生来评估激活程度。我们发现：(1)除了CD28外，通过CD4/CD8的共刺激是最佳t细胞激活所必需的；(2) VLA-4结合持续增强CD4（+）和CD8(+) t细胞活化；(3)通过VLA-4结合增强t细胞的激活在CD4/CD8结合后最为明显。这些结果证实，除了通过TCR和CD28诱导的t细胞激活之外，包括VLA-4参与在内的多种信号对于最大限度地激活t细胞是必要的。(C) 2010年美国组织相容性和免疫遗传学学会。Elsevier Inc.出版。版权所有。
The alpha(4)beta(1)integrin VLA-4 (very-late activation antigen-4) and the lineage-specific CD4 and CD8 receptors have been proposed as putative co-stimulatory receptors on T cells. To assess the relative contribution of signaling through the TCR, CD28 and these accessory molecules, we activated human T cells Using Soluble antibodies recognizing all four of these T-cell receptor classes (CD3, CD28, CD4/CD8, and VLA-4), and we assessed the degree Of activation using higher-order flow cytometry detecting intracellular Erk1/2 phosphorylation and production of IL-2 and IFN-gamma. We found that: (1) co-stimulation via CD4/CD8, in addition to CD28, is required for optimal T-cell activation; (2) VLA-4 binding consistently potentiates CD4(+) and CD8(+) T-cell activation; (3) augmentation of T-cell activation through VLA-4 binding is most pronounced following engagement of CD4/CD8. These results confirm that multiple signals, including VLA-4 engagement, are necessary for maximal T-cell activation beyond that induced via the TCR and CD28. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.