Intestinal {gamma}{delta} T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer's Patches, and Isolated Lymphoid Follicles.

摘要

Through analysis of athymic (nuu) mice carrying a transgenic gene encoding GFP instead of RAG-2 product, it has recently been reported that, in the absence of thymopoiesis, mesenteric lymph nodes and Peyer's patches (PP) but not gut cryptopatches are pivotal birthplace of mature T cells such as the thymus-independent intestinal intraepithelial T cells (IEL). To explore and evaluate this important issue, we generated nuu mice lacking all lymph nodes (LN) and PP by administration of lymphotoxin-beta receptor-Ig and TNF receptor 55-Ig fusion proteins into the timed pregnant nu/+ mice that had been mated with male nuu mice (nuu LNP(-) mice). We also generated nuu aly/aly (aly, alymphoplasia) double-mutant mice that inherently lacked all LN, PP, and isolated lymphoid follicles. Although gammadelta-IEL were slightly smaller in number than those in nuu mice, substantial colonization of gammadelta-IEL was found to take place in the intestinal epithelia of nuu LNP(-) and nuu aly/aly mice. Notably, the population size of a major CD8alphaalpha(+) gammadelta-IEL subset was maintained, the use of TCR-gamma-chain variable gene segments by these gammadelta-IEL was unaltered, and the development of cryptopatches remained intact in these nuu LNP(-) and nuu aly/aly mice. These findings indicate that all LN, including mesenteric LN, PP, and isolated lymphoid follicles, are not an absolute requirement for the development of gammadelta-IEL in athymic nuu mice.