Immunomodulatory Dendritic Cells in Intestinal Lamina Propia

CHIRDO FG; MILLINGTON OR; BEACOCK-SHARP H; MCL MOWAT A

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2005 vol. 35 p. 1831 - 1840

0014-2980

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 their isolation, purification and initial characterisation. We obtained >90% CD11c+ DC using magnetic cell sorting, of which the majority were CD11b+CD8a-, with smaller numbers of CD11b-CD8a+ and CD11b-CD8a- DC, as well as a distinct population CD11cintclass II MHClo B220+ DC. Freshly isolated LP DC expressed variable, but generally low levels of CD40, CD80 and CD86 which were upregulated by activation with LPS. LP DC were endocytic in vivo or 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 naïve recipients induced hyporesponsiveness to subsequent challenge. LP DC also expressed significant levels of mRNA for IL10 and type I IFN, but not of IL12, suggesting they may play a central and unique role in immune homeostasis in the gut.