Department of Chemistry and Biochemistry, North Dakota State University, Fargo, ND 58102, USA.
J Neuroimmunol. 2011 May;234(1-2):40-8. doi: 10.1016/j.jneuroim.2011.02.002. Epub 2011 Mar 10.
As regulation of CD8 T cell homeostasis is incompletely understood, we investigated the expression profile of the vasoactive intestinal peptide (VIP) receptors, VPAC1 and VPAC2, on CD8 T cells throughout an in vivo immune response. Herein, we show that adoptively transferred CD8 T cells responding to a Listeria monocytogenes infection significantly downregulated, functionally active VPAC1 protein expression during primary and secondary expansion. VPAC1 mRNA expression was restored during contraction and regained naïve levels in primary, but remained low during secondary, memory generation. VIP co-administration with primary infection suppressed CD8 T cell expansion (≈ 50%). VPAC2 was not detected at any time points throughout primary and secondary infections. Collectively, our data demonstrate that functionally active VPAC1 is dynamically downregulated to render expanding CD8 T cells unresponsive to VIP.
由于 CD8 T 细胞动态平衡的调控机制尚未完全阐明，我们研究了血管活性肠肽（VIP）受体 VPAC1 和 VPAC2 在体内免疫反应过程中 CD8 T 细胞上的表达谱。研究结果表明，在李斯特菌感染的适应性转移 CD8 T 细胞在初次和再次扩增过程中，功能性的 VPAC1 蛋白表达显著下调。在收缩期 VPAC1mRNA 的表达得到恢复，在初次感染时恢复到幼稚细胞水平，但在再次感染，即记忆细胞生成时仍保持低水平。VIP 与初次感染同时给药可抑制 CD8 T 细胞扩增（约 50%）。在初次和再次感染期间的任何时间点均未检测到 VPAC2。综上所述，我们的数据表明，功能性的 VPAC1 被动态下调，使正在扩增的 CD8 T 细胞对 VIP 无反应。
