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

Autori
Leithauser, Frank ; Trobonjača, Zlatko ; Moller, Peter ; Reimann, Joerg

Izvornik
Laboratory investigation (0023-6837) 81 (2001), 10; 1339-1349

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

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