Immunomodulatory dendritic cells in intestinal lamina propria

被引:191
作者
Chirdo, FG [1 ]
Millington, OR [1 ]
Beacock-Sharp, H [1 ]
Mowat, AM [1 ]
机构
[1] Western Infirm & Associated Hosp, Div Immunol Infect & Inflammat, Glasgow G11 6NT, Lanark, Scotland
基金
英国惠康基金;
关键词
dendritic cells; intestinal mucosa; lamina propria; oral tolerance;
D O I
10.1002/eji.200425882
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The lamina propria (LP) of the small intestine contains many dendritic cells (DC), which are likely to be in close contact with luminal antigens, but their role in intestinal immune responses has been overlooked. Here we show that after feeding mice ovalbumin (OVA), the majority of antigen uptake is associated with DC in the small intestinal LP, and we describe the isolation, purification and initial characterization of theses DC. We obtained > 90% CD11c(+) DC using magnetic cell sorting, of which the majority were CD11b(+)CD8a(-), with smaller numbers of CD11b(-)CD8a(+) and CD11b(-)CD8 alpha(-) DC as well as a distinct population of CD11c(int)class II MHClo B220(+) DC. Freshly isolated LP DC expressed variable but generally low levels of CD40, CD80 and CD86, which were up-regulated by activation with LPS. LP DC were endocytic in vivo and in vitro and could present antigen to OVA-specific CD4(+) T cells in vitro. Antigen-loaded LP DC from OVA-fed mice also primed specific CD4(+) T cells in vivo and in vitro, but adoptive transfer of these DC into naive recipients induced hyporesponsiveness to subsequent challenge. LP DC also expressed significant levels of mRNA for IL-10 and type I IFN, but not IL-12, suggesting they may play a central and unique role in immune homeostasis in the gut.
引用
收藏
页码:1831 / 1840
页数:10
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