The Journal of Experimental Medicine
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Published 3 November 2003. doi:10.1084/jem.20030485
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© Rockefeller University Press, 0022-1007/2003/11/1323 $5.00
The Journal of Experimental Medicine, Volume 198, Number 9, 1323-1335

L-Selectin Shedding Does Not Regulate Constitutive T Cell Trafficking but Controls the Migration Pathways of Antigen-activated T Lymphocytes

Elena Galkina1,2, Kyriakos Tanousis1, Graham Preece1, Mauro Tolaini3, Dimitris Kioussis3, Oliver Florey4, Dorian O. Haskard4, Thomas F. Tedder5 and Ann Ager1,2

1 Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
2 Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
3 Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
4 BHF Department of Cardiovascular Medicine, Hammersmith Hospital, London WW12 0NN, UK
5 Department of Immunology, Duke University Medical Center, Durham, NC 27710

Address correspondence to Ann Ager, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA UK. Phone: 44-20-8816-2479; Fax: 44-20-8906-4477; email: ann.ager{at}nimr.mrc.ac.uk

L-Selectin mediates rolling of lymphocytes in high endothelial venules (HEVs) of peripheral lymph nodes (PLNs). Cross-linking of L-selectin causes proteolytic shedding of its ectodomain, the physiological significance of which is unknown. To determine whether L-selectin shedding regulates lymphocyte migration, a mutant form that resists shedding (L{Delta}P-selectin) was engineered. Transgenic mice expressing either L{Delta}P or wild-type (WT) L-selectin on T cells were crossed with L-selectin knockout (KO) mice. The cellularity and subset composition of secondary lymphoid organs did not differ between L{Delta}P and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in L{Delta}P mice were reduced to <5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from L{Delta}P and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of L{Delta}P and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although L{Delta}P T cells transmigrated HEVs more slowly. WT, but not L{Delta}P-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and L{Delta}P T cells retained the capacity to enter PLNs from the bloodstream. These results suggest that the ability to shed L-selectin is not required for T cell recirculation and homing to PLNs. However, L-selectin shedding from antigen-activated T cells prevents reentry into PLNs.

Key Words: lymphocyte homing receptors • leukocyte rolling • vascular endothelium • matrix metalloproteinases • mice


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