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

Initial lesions in inflammatory bowel disease induced during the repopulati on of immunodeficient RAG1(-/-) mice with immunocompetent CD4(+) T cells ha ve not been previously described. In this transfer colitis model, we follow ed CD4(+) T cell repopulation in the host by injecting autofluorescent CD4( +) T cells from congenic, enhanced green fluorescent protein (eGFP)-transge nic mice. This allowed the direct, sensitive, and unambiguous histological detection of the repopulation of the intestinal tract, mesenteric lymph nod es, and spleen of the host with donor eGFP(-) CD4(+) T cells. We identified in RAG1(-/-) mice intestinal dendritic cell (DC) aggregates under the basa l crypt epithelium at the mucosa/submucosa junction from which F4/80(+) mac rophages were excluded. At Days 8 to 11 posttransfer (before colitis was ma nifest), CD4(+) T cells clustered and proliferated in CD11c(+) DC aggregate s. 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 sugges t that pathogenic T cell responses inducing inflammatory bowel disease are primed or restimulated in situ in junctional CD4(+) T cell/DC aggregates.