Fucosyltransferase VII-deficient mice with defective E-, P-, and L-selectin ligands show impaired CD4+ and CD8+ T cell migration into the skin, but normal extravasation into visceral organs.
The first step of leukocyte extravasation, leukocyte rolling, is mediated by E-, P-, and L-selectins. Mice deficient for alpha-1,3-fucosyltransferase VII (FucTVII)(-/-) are characterized by deficiency of E-, P-, and L-selectin ligand activity. This model system was used to evaluate the role of the interactions of selectins with their ligands in T and B cell responses. In the present study, FucTVII(-/-) mice showed reduced CD4+ T cell-mediated contact hypersensitivity reactions of the ears to FITC as well as reduced CD8+ T cell-mediated delayed-type hypersensitivity reactions of the footpads against lymphocytic choriomeningitis virus infection. As Langerhans cell migration to local lymph nodes as well as CD4+ and CD8+ T cell induction were found to be normal, the afferent arm of these reactions was not impaired. The reduced inflammatory reactions of the skin were due to inefficient lymphocyte extravasation into the skin. In contrast, extravasation of CD4+ and CD8+ T cells into visceral organs, such as the ovaries or the brain, was not impaired in FucTVII(-/-) mice. Elimination of vaccinia virus and of lymphocytic choriomeningitis virus from ovaries and brain, as well as elimination of tumor cells from several visceral organs was normal. Thus, interactions of selectins with their ligands are important for lymphocyte homing into the skin, but not for lymphocyte extravasation into visceral organs.
Erdmann
Iris
I
Department of Dermatology, University Hospital of Zürich, Gloriastrasse 31, 8091 Zürich, Switzerland.
Scheidegger
E Paul
EP
Koch
Frauke K
FK
Heinzerling
Lucie
L
Odermatt
Bernhard
B
Burg
Günter
G
Lowe
John B
JB
Kündig
Thomas M
TM
D000818:Animals; D001921:Brain / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics* / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D019041:L-Selectin / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology; D008024:Ligands; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology; D010053:Ovary / Q000276:immunology; D019007:P-Selectin / Q000378:metabolism; D019087:Selectins / Q000378:metabolism*; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019040:E-Selectin; D008024:Ligands; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase