The Journal of Experimental Medicine
VeriKine-HS Human Interferon-Beta Serum
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© The Rockefeller University Press, 0022-1007/1999/2/451/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 3, February 1, 1999 451-460

Articles

Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Michael D. Gunn*, Shigeru Kyuwa{ddagger}, Carmen Tam*, Terutaka Kakiuchi||, Akio Matsuzawa§, Lewis T. Williams*, and Hideki Nakano||

From the * Cardiovascular Research Institute, University of California San Francisco, San Francisco, California 94143; the {ddagger} 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

Address correspondence to Michael Dee Gunn, Division of Cardiology, Duke University Medical Center, Box 3547, Durham, NC 27710. Phone: 919-681-5072; Fax: 919-684-8591; E-mail: michael.gunn{at}duke.edu

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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