Distinctive immune surveillance of intestinal mucosal tissues

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It has been demonstrated that mesenteric lymph nodes (MLN) but not gut cryptopatches (CP) are pivotal birthplace of thymus-independent intestinal intraepithelial T cells (IEL) in athymic nu/nu mice (J. Exp. Med. 197 : 333, 2003). To explore and evaluate this important issue, we generated nu/nu mice lacking all LN and Peyer's patches (PP) by administration of lymphotoxin (LT)β-R-Ig and TNF-R55-Ig fusion proteins into 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 lacking all LN, PP and isolated lymphoid follicles (ILF). Although γδ-IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of γδ-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 major CD8αα^+ γδ-IEL subset was maintained, use of TCR-y-chain variable gene segments by these γδ-IEL was unaltered and the development of CP remained intact in these nu/nu LNP-and nu/nu aly/aly mice. These and other findings indicate that all LN including MLN, PP and ILF are not an absolute requirement for the development of γδ-IEL but instead support the concept that gut CP generate progenitor γδ-IEL in the athymic nu/nu condition (J. Immunol. 174:1906,2005).