A NOVEL MUTANT-GENE INVOLVED IN T-LYMPHOCYTE-SPECIFIC HOMING INTO PERIPHERAL LYMPHOID ORGANS ON MOUSE-CHROMOSOME-4

Previously, we have shown a mutant mouse DDD/1 with T-cell-specific ho ming defect that is regulated by an autosomal recessive gene, pit (pau city of lymph node T cells), and seems to be caused by lymph node (LN) stromal cells. In the present study, immunohistochemical analysis sho wed unusual distribution of T cells in LN, Peyer's patches (PP), and s pleen from plt/plt, 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, ba sed on the experiments in which labelled T cells were injected intrave nously and detected in the tissues. Analysis of surface L-selectin and CD44 suggested that T cells with memory phenotype, probably from affe rent lymphatics, recruit into plt/plt LN. Linkage mapping by simple-se quence length polymorphism of genomic DNA from 190 backcross progenies produced by intercrossing with MSM/Ms, linked pit most closely with D 4Mit237, and localized at 24.7 cM from cetromere on chromosome 4. We d iscuss the possibility that a wild-type gene on pit locus encodes a ch emokine inducing T-cell-specific homing into peripheral lymphoid tissu es. (C) 1998 by The American Society of Hematology.