L-selectin shedding does not regulate constitutive T cell trafficking but controls the migration pathways of antigen-activated T lymphocytes.
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 (LdDeltaP-selectin) was engineered. Transgenic mice expressing either LDeltaP 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 LDeltaP and WT mice, however, they were different from C57BL/6. Plasma levels of soluble L-selectin in LDeltaP mice were reduced to <5% of WT and C57BL/6 mice. The rolling properties of T lymphocytes from LDeltaP and WT mice on immobilized L-selectin ligands were similar. Furthermore, similar numbers of LDeltaP and WT T lymphocytes were recruited from the bloodstream into PLNs in mice, although LDeltaP T cells transmigrated HEVs more slowly. WT, but not LDeltaP-selectin, underwent rapid, metalloproteinase-dependent shedding after TCR engagement, and LDeltaP 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.
Division of Cellular Immunology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
Elena
E
Galkina
Kyriakos
K
Tanousis
Graham
G
Preece
Mauro
M
Tolaini
Dimitris
D
Kioussis
Oliver
O
Florey
Dorian O
DO
Haskard
Thomas F
TF
Tedder
Ann
A
Ager
D000818:Animals; D000941:Antigens / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019041:L-Selectin / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D019041:L-Selectin