L-Selectin Shedding Does Not Regulate Constitutive T Cell Trafficking but Controls the Migration Pathways of Antigen-activated T Lymphocytes (original) (raw)
Article| November 03 2003
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
2Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
3Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
3Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
4BHF Department of Cardiovascular Medicine, Hammersmith Hospital, London WW12 0NN, UK
Search for other works by this author on:
4BHF Department of Cardiovascular Medicine, Hammersmith Hospital, London WW12 0NN, UK
Search for other works by this author on:
5Department of Immunology, Duke University Medical Center, Durham, NC 27710
Search for other works by this author on:
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
2Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Search for other works by this author on:
Elena Galkina
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
2Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Kyriakos Tanousis
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Graham Preece
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Mauro Tolaini
3Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Dimitris Kioussis
3Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
Oliver Florey
4BHF Department of Cardiovascular Medicine, Hammersmith Hospital, London WW12 0NN, UK
Dorian O. Haskard
4BHF Department of Cardiovascular Medicine, Hammersmith Hospital, London WW12 0NN, UK
Thomas F. Tedder
5Department of Immunology, Duke University Medical Center, Durham, NC 27710
Ann Ager
1Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
2Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
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: [email protected]
E. Galkina and K. Tanousis contributed equally to this work.
Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate-succinimidyl ester; CMTMR, 5-(and 6)-([{4-chloromethyl}benzoyl]amino) tetramethylrhodamine; HEV, high endothelial venule; MLN, mesenteric LN; MMP, matrix metalloproteinase; MPR, membrane proximal region; PLN, peripheral LN; sL-selectin, soluble L-selectin; PPME, polyphosphomannan ester.
Received: March 27 2003
Revision Received: July 11 2003
Accepted: September 16 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (9): 1323–1335.
Revision Received:
July 11 2003
Accepted:
September 16 2003
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 (LΔP-selectin) was engineered. Transgenic mice expressing either LΔP 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 LΔP and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in LΔP mice were reduced to <5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from LΔP and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of LΔP and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although LΔP T cells transmigrated HEVs more slowly. WT, but not LΔP-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and LΔP 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.
The Rockefeller University Press
2003
You do not currently have access to this content.
Sign in
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Username (Note: This may be your email address.) ?
Password
Could not validate captcha. Please try again.
8,901 Views
113 Web of Science