Intestinal gamma delta T cells develop in mice lacking thymus, all lymph nodes, Peyer's patches, and isolated lymphoid follicles.
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-beta 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 gammadelta-IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of gammadelta-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 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 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 gammadelta-IEL in athymic nu/nu mice.
Nonaka
Satoshi
S
Department of Microbiology and Immunology, Keio University School of Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Naito
Tomoaki
T
Chen
Hao
H
Yamamoto
Masafumi
M
Moro
Kazuyo
K
Kiyono
Hiroshi
H
Hamada
Hiromasa
H
Ishikawa
Hiromichi
H
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008198:Lymph Nodes / Q000002:abnormalities; D008221:Lymphoid Tissue / Q000002:abnormalities* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000002:abnormalities / Q000276:immunology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000002:abnormalities; D019076:Transgenes / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D019009:Proto-Oncogene Proteins c-kit