Abstract：
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.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Nemoto Y,Kanai T,Makita S,Okamoto R,Totsuka T,Takeda K,Watanabe Mdoi
10.1053/j.gastro.2006.10.035subject
Has Abstractpub_date
2007-01-01 00:00:00pages
176-89issue
1eissn
0016-5085issn
1528-0012pii
S0016-5085(06)02269-4journal_volume
132pub_type
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