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Intestinal T Cells Develop in Mice Lacking Thymus, All Lymph Nodes, Peyer’s Patches, and Isolated Lymphoid Follicles¹

Satoshi Nonaka^*, Tomoaki Naito^*, Hao Chen^*, Masafumi Yamamoto, Kazuyo Moro^*, Hiroshi Kiyono, Hiromasa Hamada^* and Hiromichi Ishikawa^2,*

^* Department of Microbiology and Immunology, Keio University School of Medicine, and Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and Department of Oral Medicine, Nihon University School of Dentistry, Chiba, Japan

Through analysis of athymic (nu/nu) 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 nu/nu mice lacking all lymph nodes (LN) and PP by administration of lymphotoxin- receptor-Ig and TNF receptor 55-Ig fusion proteins into the timed pregnant nu/+ mice that had been mated with male nu/nu mice (nu/nu LNP^– mice). We also generated nu/nu aly/aly (aly, alymphoplasia) double-mutant mice that inherently lacked all LN, PP, and isolated lymphoid follicles. Although -IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of -IEL was found to take place in the intestinal epithelia of nu/nu LNP^– and nu/nu aly/aly mice. Notably, the population size of a major CD8⁺ -IEL subset was maintained, the use of TCR--chain variable gene segments by these -IEL was unaltered, and the development of cryptopatches remained intact in these nu/nu LNP^– and nu/nu 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 -IEL in athymic nu/nu mice.

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