Genetic defect in T lymphocyte-specific homing into peripheral lymph nodes.
Lymphocytes circulating in the bloodstream home into lymph nodes (LN). T cells predominate in peripheral LN (PLN) and B cells in spleen or mucosal tissue, e.g. Peyer's patches (PP). DDD/1 mice are unique in marked paucity of LN cells, especially T cells. T cell frequency in PLN was 20-40% in this strain, compared to 60-80% in others. Immunohistochemistry confirmed the low density of T cells in the subcortical area but normal colonization of B cells in cortical area in PLN of DDD/1. In contrast, the T cell content of peripheral blood and spleen was higher in DDD/1 but that in PP was not significantly different compared to other strains. It was thus concluded that this abnormality in DDD/1 results from a homing defect of T cells into PLN but not from lymphopenia. Genetical analysis showed that the defect in T cell-specific homing was regulated by a single autosomal recessive gene, tentatively designated plt (paucity of lymph node T cells). Reciprocal bone marrow transplantation indicated that the plt phenotype may arise from some defect in PLN stroma but not in lymphocytes. An in vivo homing assay using fluorescence-labeled lymphocytes demonstrated that the homing defect was specific for T cells but not for B cells. A Stamper-Woodruff assay revealed that the binding between lymphocytes and PLN high endothelial venules was normal and that L-selectin and its ligand, peripheral node vascular addressin (PNAd), were expressed and functioned normally in DDD/1. These results taken together indicate that the T cell-specific homing into PLN is disturbed at a post-adhesion stage in DDD/1. The product of the plt locus may play a pivotal role at this stage.
Nakano
H
H
Laboratory Animal Research Center, University of Tokyo, Japan.
Tamura
T
T
Yoshimoto
T
T
Yagita
H
H
Miyasaka
M
M
Butcher
E C
EC
Nariuchi
H
H
Kakiuchi
T
T
Matsuzawa
A
A
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D005260:Female; D019041:L-Selectin / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010581:Peyer's Patches / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology*
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D019041:L-Selectin; D017493:Leukocyte Common Antigens