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Center for Experimental Medicine and
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; and the || Department of Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan
Secondary lymphoid organ chemokine (SLC) is expressed in high endothelial venules and in T cell zones of spleen and lymph nodes (LNs) and strongly attracts naive T cells. In mice homozygous for the paucity of lymph node T cell (plt) mutation, naive T cells fail to home to LNs or the lymphoid regions of spleen. Here we demonstrate that expression of SLC is undetectable in plt mice. In addition to the defect in T cell homing, we demonstrate that dendritic cells (DCs) fail to accumulate in spleen and LN T cell zones of plt mice. DC migration to LNs after contact sensitization is also substantially reduced. The physiologic significance of these abnormalities in plt mice is indicated by a markedly increased sensitivity to infection with murine hepatitis virus. The plt mutation maps to the SLC locus; however, the sequence of SLC introns and exons in plt mice is normal. These findings suggest that the abnormalities in plt mice are due to a genetic defect in the expression of SLC and that SLC mediates the entry of naive T cells and antigen-stimulated DCs into the T cell zones of secondary lymphoid organs.
Key Words: CC chemokines cellular immunity leukocyte chemotaxis T lymphocytes mutation
Abbreviations used: AP, alkaline phosphatase; DC, dendritic cell; ELC, EBV-induced molecule 1 ligand chemokine; HEV, high endothelial venule; HPF, high power field; HRP, horseradish peroxidase; MHV, murine hepatitis virus; PerCP, peridinine chlorophyll protein; plt, paucity of lymph node T cells; PP, Peyer's patch; SA, streptavidin; SLC, secondary lymphoid organ chemokine.
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