HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fukunaga, A. Articles by Ullrich, S. E. Search for Related Content PubMed PubMed Citation Articles by Fukunaga, A. Articles by Ullrich, S. E.

Dermal Dendritic Cells, and Not Langerhans Cells, Play an Essential Role in Inducing an Immune Response¹

Department of Immunology and Center for Cancer Immunology Research, M.D. Anderson Cancer Center, University of Texas, Houston, TX 77030

Langerhans cells (LCs) serve as epidermal sentinels of the adaptive immune system. Conventional wisdom suggests that LCs encounter Ag in the skin and then migrate to the draining lymph nodes, where the Ag is presented to T cells, thus initiating an immune response. Platelet-activating factor (PAF) is a phospholipid mediator with potent biological effects. During inflammation, PAF mediates recruitment of leukocytes to inflammatory sites. We herein tested a hypothesis that PAF induces LC migration. Applying 2,4-dinitro-1-fluorobenzene (DNFB) to wild-type mice activated LC migration. In contrast, applying DNFB to PAF receptor-deficient mice or mice injected with PAF receptor antagonists failed to induce LC migration. Moreover, after FITC application the appearance of hapten-laden LCs (FITC⁺, CD11c⁺, Langerin⁺) in the lymph nodes of PAF receptor-deficient mice was significantly depressed compared with that found in wild-type mice. LC chimerism indicates that the PAF receptor on keratinocytes but not LCs is responsible for LC migration. Contrary to the diminution of LC migration in PAF receptor-deficient mice, we did not observe any difference in the migration of hapten-laden dermal dendritic cells (FITC⁺, CD11c⁺, Langerin^–) into the lymph nodes of PAF receptor-deficient mice. Additionally, the contact hypersensitivity response generated in wild-type or PAF receptor-deficient mice was identical. Finally, dermal dendritic cells, but not LCs isolated from the draining lymph nodes after hapten application, activated T cell proliferation. These findings suggest that LC migration may not be responsible for the generation of contact hypersensitivity and that dermal dendritic cells may play a more important role.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Cancer Institute (CA75575, CA88943, and CA112660). S.N.B. was supported by a C. J. Martin Fellowship (307726) from the National Health and Medical Research Council of Australia. The animal, histology, and flow cytometry facilities at the M.D. Anderson Cancer Center are supported in part by a core grant from the National Cancer Institute (CA16672).

² Current address: Dermatology Research Laboratories, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital, University of Sydney, Sydney, New South Wales, Australia.

³ Address correspondence and reprint requests to Dr. Stephen E. Ullrich, Department of Immunology-902, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail address: sullrich{at}mdanderson.org

⁴ Abbreviations used in this paper: DC, dendritic cell; LC, Langerhans cell; CHS, contact hypersensitivity; dDC, dermal DC; PAF, platelet-activating factor; PAFR, PAF receptor; DNFB, 2,4-dinitro-1-fluorobenzene; c-PAF, carbamyl-PAF; WT, wild type; BM, bone marrow; OXA, 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; Ct, threshold cycle.