Budget Amount *help |
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1996: ¥8,600,000 (Direct Cost: ¥8,600,000)
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Research Abstract |
We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches ; CPs) and can be first detected at 14-1 7 days after birth. A large fraction of lymphocytes in CPs expresses c-kit, 1L-7R, Thy1 and a common leukocyte antigen, LFA-1, whereas most of them remain CD3ィイD1-ィエD1, TCRαβィイD1-ィエD1, TCRγδィイD1-ィエD1, slgMィイD1-ィエD1 and B220ィイD1-ィエD1. The population size of 1L-2RαィイD1+ィエD1, HASィイD1+ィエD1 and Pgp-1ィイD1+ィエD1 subsets is variable (20-50%) and the composition of CD8ィイD1+ィエD1, Ly-1ィイD1+ィエD1 and CD4ィイD1+ィエD1 subsets is smaller but also variable (3-20%). In the small intestine, CPs do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CPs is higher than that in Peyer's patches (PPs)
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, is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CPs remain the same in aged mice (>114 wks) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PPs, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CPs. Finally, CPs are virtually absent in lamina propria of 1L-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CPs are present in germ-free mice and in athymic (nu/nu), SCID, TCRβ×δ ィイD1-/-ィエD1 RAG-2ィイD1-/-ィエD1, PP-deficient (aly/aly), stem cell factor (Sl/SlィイD1dィエD1) and c-kit (W/WィイD1vィエD1) mutant mice. Taking all of these results together, CPs are the first identification of gut-associated murine lymphoid tissues where the generation of 1L-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning. Less
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