Clustering of colonic lamina propria CD4(+) T cells to subepithelial dendritic cell aggregates precedes the development of colitis in a murine adoptive transfer model

Lab Invest. 2001 Oct;81(10):1339-49. doi: 10.1038/labinvest.3780348.


Initial lesions in inflammatory bowel disease induced during the repopulation of immunodeficient RAG1(-/-) mice with immunocompetent CD4(+) T cells have not been previously described. In this transfer colitis model, we followed CD4(+) T cell repopulation in the host by injecting autofluorescent CD4(+) T cells from congenic, enhanced green fluorescent protein (eGFP)-transgenic mice. This allowed the direct, sensitive, and unambiguous histological detection of the repopulation of the intestinal tract, mesenteric lymph nodes, and spleen of the host with donor eGFP(+) CD4(+) T cells. We identified in RAG1(-/-) mice intestinal dendritic cell (DC) aggregates under the basal crypt epithelium at the mucosa/submucosa junction from which F4/80(+) macrophages were excluded. At Days 8 to 11 posttransfer (before colitis was manifest), CD4(+) T cells clustered and proliferated in CD11c(+) DC aggregates. T cell clustering was most pronounced in the cecum where histologically overt colitis became manifest 5 to 10 days later. Junctional DC aggregates were thus prevalent in the triggering phase of the disease. The data suggest that pathogenic T cell responses inducing inflammatory bowel disease are primed or restimulated in situ in junctional CD4(+) T cell/DC aggregates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Adhesion
  • Cell Communication / immunology
  • Colon / immunology
  • Colon / pathology*
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology*
  • Inflammatory Bowel Diseases / etiology
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology*
  • Mice