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经抗原致敏的脾脏CD8 + T细胞会阻碍口服抗原诱导的过敏性腹泻的发展。

Antigen-primed splenic CD8+ T cells impede the development of oral antigen-induced allergic diarrhea.

作者信息

Yamada Akiko, Ohshima Yusei, Yasutomi Motoko, Ogura Kazumasa, Tokuriki Shuko, Naiki Hironobu, Mayumi Mitsufumi

机构信息

Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

出版信息

J Allergy Clin Immunol. 2009 Apr;123(4):889-94. doi: 10.1016/j.jaci.2008.12.1115. Epub 2009 Feb 6.

Abstract

BACKGROUND

Although CD4+ T-cell populations are thought to be involved in the pathophysiology of food allergy and oral tolerance, the role of CD8+ T cells remains uncertain.

OBJECTIVE

We analyzed regulatory effects of adoptively transferred CD8+ T cells on the development of allergic diarrhea in antigen-sensitized mice that had a significantly reduced number of conventional TCRalphabeta+ CD8+ T cells.

METHODS

Ovalbumin-specific T-cell receptor transgenic mice were systemically sensitized to ovalbumin. Splenic CD8+ T cells purified from ovalbumin-sensitized or nonsensitized wild-type mice or IL-10 knockout mice were adoptively transferred to ovalbumin-sensitized ovalbumin-specific T-cell receptor transgenic mice. Allergic diarrhea induced by oral administration of ovalbumin, ovalbumin-specific immunoglobulin production, and cytokine production in intestines and mesenteric lymph nodes were assessed.

RESULTS

Adoptive transfer of splenic CD8+ T cells from ovalbumin-primed mice, but not from nonprimed mice, suppressed the development of allergic diarrhea, which was associated with in vivo increased IL-10 mRNA expression and in vitro antigen-specific IL-10 production by mesenteric lymph node cells. Upregulation of serum ovalbumin-specific IgE was not suppressed by ovalbumin-primed CD8+ T-cell transfer. Although administration of IL-10 before ovalbumin challenge failed to alleviate allergic diarrhea, transfer of splenic CD8+ T cells from IL-10 knockout mice showed diminished preventive effects.

CONCLUSION

Systemic immunization with allergen simultaneously induces regulatory CD8+ T cells that can inhibit the development of allergic diarrhea. IL-10 production by regulatory CD8+ T cells appears to be partially involved in these inhibitory mechanisms.

摘要

背景

尽管CD4+ T细胞群体被认为参与食物过敏和口服耐受的病理生理过程,但CD8+ T细胞的作用仍不明确。

目的

我们分析了过继转移的CD8+ T细胞对传统TCRαβ+ CD8+ T细胞数量显著减少的抗原致敏小鼠过敏性腹泻发展的调节作用。

方法

卵清蛋白特异性T细胞受体转基因小鼠经全身致敏于卵清蛋白。从卵清蛋白致敏或未致敏的野生型小鼠或IL-10基因敲除小鼠中纯化的脾CD8+ T细胞过继转移至卵清蛋白致敏的卵清蛋白特异性T细胞受体转基因小鼠。评估口服卵清蛋白诱导的过敏性腹泻、卵清蛋白特异性免疫球蛋白产生以及肠道和肠系膜淋巴结中的细胞因子产生情况。

结果

过继转移来自卵清蛋白预致敏小鼠而非未预致敏小鼠的脾CD8+ T细胞可抑制过敏性腹泻的发展,这与体内IL-10 mRNA表达增加以及肠系膜淋巴结细胞体外抗原特异性IL-10产生有关。卵清蛋白预致敏的CD8+ T细胞转移未抑制血清卵清蛋白特异性IgE的上调。尽管在卵清蛋白攻击前给予IL-10未能减轻过敏性腹泻,但过继转移来自IL-10基因敲除小鼠的脾CD8+ T细胞显示出减弱的预防作用。

结论

用变应原进行全身免疫可同时诱导调节性CD8+ T细胞,其可抑制过敏性腹泻的发展。调节性CD8+ T细胞产生的IL-10似乎部分参与了这些抑制机制。

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