Foxp3-expressing CD103+ regulatory T cells accumulate in dendritic cell aggregates of the colonic mucosa in murine transfer colitis

Am J Pathol. 2006 Jun;168(6):1898-909. doi: 10.2353/ajpath.2006.050228.

Abstract

Little is known of the anatomical compartmentalization of colitogenic or regulatory T-cell responses in the murine transfer colitis model. Therefore, we analyzed the putative function of large intestinal dendritic cell (DC) aggregates, to which donor CD4+ T cells selectively home before colitis becomes manifest. The co-stimulatory molecules MHC-II, CD40, CD80, and CD86 were expressed in DC aggregates. IL-23 was primarily absent from DC aggregates at all stages of disease but was expressed at high levels in the severely inflamed lamina propria. Interferon-gamma was up-regulated in the lamina propria during early and advanced disease, whereas in DC aggregates it was detectable to a significant degree only in fully developed colitis. In contrast, Foxp3, a marker of regulatory T cells, was expressed in DC aggregates on T-cell transfer, coinciding with the appearance of CD103+ CD25- T cells in these clusters. Foxp3 was enriched in the CD103+ T-cell fraction isolated from the lamina propria of diseased mice. T-cell grafts depleted of CD103+ T cells generated similar numbers of colonic CD103+ T cells as unfractionated T cells. We conclude that DC aggregates are structures involved in the expansion and/or differentiation of CD103+ CD25- CD4+ Foxp3-expressing regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis*
  • CD4-Positive T-Lymphocytes / metabolism
  • Colitis / metabolism
  • Colitis / pathology*
  • Colon / cytology*
  • Dendritic Cells / cytology*
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Integrin alpha Chains / biosynthesis*
  • Intestinal Mucosa / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • T-Lymphocytes, Regulatory / cytology*

Substances

  • Antigens, CD
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Integrin alpha Chains
  • alpha E integrins
  • Green Fluorescent Proteins