SummaryWe 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 nmcosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction oflymphocytes in CP expresses c-kit, IL-7R, Thyl and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR oil3-, TCR "yS-, slgM-, and B220-. The population size of IL-2Ikot +, HSA + and Pgp-1 + subsets is variable (20-50%) and the composition of CD8 +, Ly-1 +, and CD4 + subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD1 lc/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (>114 wk) 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 PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR [3 • 8-/-, RAG-2 -/-, PP-deficient (aly/aly), stem cell factor (S1/S1 a) and c-kit (W/W v) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.

Cryptopatches (CPs) are part of the murine intestinal immune compartment. Cells isolated from CPs of the small intestine that were c-kit positive (c-kit+) but lineage markers negative (Lin-) gave rise to T cell receptor (TCR) alphabeta and TCR gammadelta intestinal intraepithelial T cells after in vivo transfer or tissue engraftment into severe combined immunodeficient mice. In contrast, cells from Peyer's patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit+Lin- cells, failed to do so. These findings and results of electron microscopic analysis provide evidence of a local intestinal T cell precursor that develops in the CPs.