1. ¹Department of Pathology, University of Ulm, Ulm, Germany
2. ²Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany

Correspondence: Dr. Frank Leithäuser, Department of Pathology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany. E-mail: frank.leithaeuser@medizin.uni-ulm.de

Received 3 April 2001.

Abstract

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.