CD4+ T Cells Migrate into Inflamed Skin Only If They Express Ligands for E- and P-Selectin

Author:

Tietz Wolfgang12,Allemand Yvonne12,Borges Eric32,von Laer Dorothea42,Hallmann Ruppert52,Vestweber Dietmar32,Hamann Alf12

Affiliation:

1. *Department of Immunology, Medical Clinic, University Hospital Eppendorf, Hamburg, Germany;

2. A. Hamann, F. Austrup, W. Tietz, and D. Jablonski-Westrich. Activation induces rapid and profound alterations in the trafficking of T cells. Submitted for publication.

3. †Institute of Cell Biology, University of Münster, Münster, Germany;

4. ‡Heinrich Pette Institute, Hamburg, Germany; and

5. §Institute for Experimental Medicine, University of Erlangen-Nürnberg, Erlangen, Germany

Abstract

Abstract Previous data suggested a role of endothelial selectins in skin homing of lymphocytes. In the current study, we have analyzed the expression and functional role of E-and P-selectin ligands on CD4+ T cells induced in vivo upon skin sensitization, using soluble selectin-Ig chimera and blocking Abs. Only low numbers of CD4+ cells expressing significant levels of E- or P-selectin ligands were present in s.c. lymph nodes of untreated mice (0.5–1.5% and 2–4%, respectively). Induction of a delayed-type hypersensitivity reaction increased the percentage of E-selectin-binding CD4+ cells in the draining lymph nodes up to 6 to 9% and that of P-selectin-binding cells up to 14%. The majority of E- and P-selectin-binding cells displayed an activated phenotype as judged by the increase in IL-2R, CD71, or cell size. The populations of E- and P-selectin-binding cells were largely overlapping; all E-selectin-binding cells also bound to P-selectin, whereas only a subfraction of P-selectin-binding cells reacted with E-selectin. Both E- and P-selectin-binding CD4+ cells, isolated by FACS, efficiently migrated into inflamed, but not normal skin, whereas P- or E-selectin ligand-negative CD4+ T cells did not. Abs against one of the two endothelial selectins partially inhibited the entry of isolated, ligand-positive cells, whereas a combination of Abs against both selectins almost completely abrogated skin homing. These data indicate that the expression of functional ligands for E- and for P-selectin is essential for homing of CD4+ T cells into the inflamed skin.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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