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© The Rockefeller University Press, 0021-9525/1997//1137 $5.00
The Journal of Cell Biology, Volume 137, Number 5, , 1997 1137-1147

Article

An Essential Role for CD44 Variant Isoforms in Epidermal Langerhans Cell and Blood Dendritic Cell Function



Johannes M. Weiss*, Jonathan Sleeman§, Andreas C. Renkl*, Henning Dittmar*, Christian C. Termeer*, Sabine Taxis*, Norma Howells§, Martin Hofmann§, Gabriele Köhler{ddagger}, Erwin Schöpf*, Helmut Ponta§, Peter Herrlich§, and Jan C. Simon*

* Department of Dermatology, {ddagger} Department of Pathology, Freiburg University, D-79104 Freiburg, Germany; and § Institute of Genetics, Forschungszentrum Karlsruhe, Germany

Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC) leave peripheral organs and home to lymph nodes via the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors to lymph nodes, we explored the expression of CD44 proteins on migrating LC and DC. We show that upon antigen contact, LC and DC upregulate pan CD44 epitopes and epitopes encoded by variant exons v4, v5, v6, and v9. Antibodies against CD44 epitopes inhibit the emigration of LC from the epidermis, prevent binding of activated LC and DC to the T cell zones of lymph nodes, and severely inhibit their capacity to induce a delayed type hypersensitivity reaction to a skin hapten in vivo. Our results demonstrate that CD44 splice variant expression is obligatory for the migration and function of LC and DC.

Abbreviations used in this paper: ANOVA, analysis of variance; CD44v, CD44 variant; DC, dendritic cells; DTH, delayed type hypersensitivity; ECM, extracellular matrix; GM-CSF, granulocyte macrophage colony stimulating factor; HA, hyaluronate; LC, Langerhans cells; LN, lymph nodes; MFI, mean fluorescence intensity.

Address all correspondence to Johannes M. Weiss, Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany. Tel.: 49 761-270-6831. Fax: 49 761-270-6829.


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