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Publication : Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis.

First Author  Nemoto Y Year  2007
Journal  Gastroenterology Volume  132
Issue  1 Pages  176-89
PubMed ID  17241870 Mgi Jnum  J:128223
Mgi Id  MGI:3766523 Doi  10.1053/j.gastro.2006.10.035
Citation  Nemoto Y, et al. (2007) Bone marrow retaining colitogenic CD4+ T cells may be a pathogenic reservoir for chronic colitis. Gastroenterology 132(1):176-89
abstractText  BACKGROUND & AIMS: Although bone marrow (BM) is known as a primary lymphoid organ, it also is known to harbor memory T cells, suggesting that this compartment is a preferential site for migration and/or selective retention of memory T cells. We here report the existence and the potential ability to induce colitis of the colitogenic BM CD4+ memory T cells in murine colitis models. METHODS: We isolated BM CD4+ T cells obtained from colitic severe combined immunodeficient mice induced by the adoptive transfer of CD4+ CD45RB(high) T cells and colitic interleukin (IL)-10(-/-) mice that develop colitis spontaneously, and analyzed the surface phenotype, cytokine production, and potential activity to induce colitis. Furthermore, we assessed the role of IL-7 to maintain the colitogenic BM CD4+ T cells. RESULTS: A high number of CD4+ T cells reside in the BM of colitic severe combined immunodeficient mice and diseased IL-10(-/-) mice, and they retain significant potential to induce type-1 T helper-mediated colitis in an IL-7-dependent manner. These resident BM CD4+ T cells have an effector memory (T(EM); CD44(high)CD62L(-)IL-7R(high)) phenotype and preferentially are attached to IL-7-producing BM cells. Furthermore, the accumulation of BM CD4+ T(EM) cells was decreased significantly in IL-7-deficient recipients reconstituted with the colitogenic lamina propria CD4+ T(EM) cells. CONCLUSIONS: Collectively, these findings suggest that BM-retaining colitogenic CD4+ memory T cells in colitic mice play a critical role as a reservoir for persisting lifelong colitis.
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