A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4

Abstract

Previously, we have shown a mutant mouse DDD/1 with T-cell-specific homing defect that is regulated by an autosomal recessive gene, pit (paucity of lymph node T cells), and seems to be caused by lymph node (LN) stromal cells. In the present study, immunohistochemical analysis showed unusual distribution of T cells in LN, Peyer's patches (PP), and spleen from pit/pit, probably due to the failure of T cells to migrate from blood into the T-cell zone in LN or PP, or into the spleen white pulp across high endothelial venule or marginal zone, respectively, based on the experiments in which labelled T cells were injected intravenously and detected in the tissues. Analysis of surface L-selectin and CD44 suggested that T cells with memory phenotype, probably from afferent lymphatics, recruit into pit/pit LN. Linkage mapping by simple-sequence length polymorphism of genomic DNA from 190 backcross progenies produced by intercrossing with MSM/Ms, linked pit most closely with D4Mit237, and localized at 24.7 cM from cetromere on chromosome 4. We discuss the possibility that a wild-type gene on pit locus encodes a chemokine inducing T-cell-specific homing into peripheral lymphoid tissues.