Mathew R C, Cook G A, Blum A M, Metwali A, Felman R, Weinstock J V
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
J Immunol. 1992 Jun 1;148(11):3572-7.
In murine schistosomiasis, granulomas form around ova deposited in the liver and intestines of infected mice. The granulomas have eosinophils that produce vasoactive intestinal peptide (VIP) and T cells that display VIP receptors. IL-5 is a lymphokine important for the development and maturation of eosinophils. It seemed plausible that VIP, released from eosinophils, may interact with lymphocyte VIP receptors and modulate IL-5 production as part of a feedback regulatory circuit. Thus, we determined whether granuloma T cells make IL-5 and whether VIP modulates IL-5 production. Isolated granuloma cells enriched for T lymphocytes spontaneously released IL-5. Culture of these cells in the presence of VIP increased IL-5 secretion. Spleen cells were also studied. Spleen cells from infected mice did not spontaneously release IL-5 or express IL-5 mRNA and VIP did not stimulate these resting spleen cells to produce this IL. However, these cells did express IL-5 mRNA and secreted IL-5 in response to Con A or soluble egg Ag. VIP could not appreciably modulate IL-5 release when cells were cultured with VIP and the Ag or mitogen. Spleen cells washed free of Con A ceased IL-5 secretion within 24 h. These preactivated splenic T cells resumed vigorous IL-5 secretion in response to either Con A or VIP. Yet only Con A prominently induced IL-5 mRNA expression. VIP was an effective stimulus at concentrations equal to or above the kDa of the VIP receptor on both splenic and granuloma T cells (10(-8) M). It is concluded that, in murine schistosomiasis, VIP invokes IL-5 release from activated T cells that are not undergoing immediate TCR stimulation.
在小鼠血吸虫病中，肉芽肿形成于沉积在受感染小鼠肝脏和肠道中的虫卵周围。这些肉芽肿含有产生血管活性肠肽（VIP）的嗜酸性粒细胞和表达VIP受体的T细胞。白细胞介素-5（IL-5）是一种对嗜酸性粒细胞的发育和成熟很重要的淋巴因子。嗜酸性粒细胞释放的VIP可能与淋巴细胞VIP受体相互作用，并调节IL-5的产生，作为反馈调节回路的一部分，这似乎是合理的。因此，我们确定肉芽肿T细胞是否产生IL-5以及VIP是否调节IL-5的产生。富集T淋巴细胞的分离肉芽肿细胞自发释放IL-5。在VIP存在下培养这些细胞可增加IL-5的分泌。还对脾细胞进行了研究。感染小鼠的脾细胞不会自发释放IL-5或表达IL-5 mRNA，VIP也不会刺激这些静止的脾细胞产生这种白细胞介素。然而，这些细胞确实表达IL-5 mRNA，并在接触刀豆蛋白A（Con A）或可溶性虫卵抗原时分泌IL-5。当细胞与VIP和抗原或丝裂原一起培养时，VIP不能明显调节IL-5的释放。洗去Con A的脾细胞在24小时内停止IL-5分泌。这些预先激活的脾T细胞在接触Con A或VIP后恢复大量IL-5分泌。然而，只有Con A能显著诱导IL-5 mRNA表达。在脾T细胞和肉芽肿T细胞上，VIP在等于或高于VIP受体的kDa（10^(-8) M）的浓度下是一种有效的刺激物。得出的结论是，在小鼠血吸虫病中，VIP可促使未受到即时TCR刺激的活化T细胞释放IL-5。
