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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maeda, A. Articles by Schwarz, T. Search for Related Content PubMed PubMed Citation Articles by Maeda, A. Articles by Schwarz, T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB 1-FLUORO-2,4-DINITROBENZENE

Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells¹

Akira Maeda^*,, Agatha Schwarz^*, Ann Bullinger, Akimichi Morita, David Peritt and Thomas Schwarz^2,*

^* Department of Dermatology, University Kiel, Kiel, Germany; Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and Therakos, Incorporated, Exton, PA 19341

Extracorporeal photopheresis (ECP) is used to treat immune-mediated diseases including transplant rejection and graft-vs-host-disease. An experimental murine model of ECP utilizing contact hypersensitivity (CHS) revealed that ECP inhibits the sensitization of CHS and induces regulatory T cells (Treg). In this study, we find that ECP inhibits not only the sensitization but also the effector phase of CHS, although Treg only inhibited sensitization. IL-10 was determined to be a critical component of the effector phase inhibition and also a driving force in developing Treg. Thus, we propose that the inhibition of the effector phase of CHS by ECP is a process that does not require Treg but may be mediated via enhanced IL-10 as suggested by the use of IL-10-deficient mice. This suggests that ECP has at least two mechanisms of action, one inhibiting the effector phase of CHS and one generating Treg, which in turn can inhibit CHS sensitization and is responsible for the transferable protection. Together, this may help explain the clinical benefits of ECP in prophylactic, acute, and therapeutic settings.

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 study was supported by a grant from the German Research Foundation (SCHW 1177/1-2) and a grant from Therakos, a Johnson & Johnson Company (to T.S., A.B., and D.P.).

² Address correspondence and reprint requests to Dr. Thomas Schwarz, Department of Dermatology, University Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. E-mail address: tschwarz{at}dermatology.uni-kiel.de

³ Abbreviations used in this paper: ECP, extracorporeal photopheresis; CHS, contact hypersensitivity; DNBS, dinitrofluorobenzene sulfonic acid; DNFB, 2,4-dinitro-1-fluorobenzene; Treg, regulatory T cell; ECP-Treg, ECP-induced Treg; GvHD, graft-vs-host-disease; 8-MOP, 8-methoxypsoralen; WT, wild type; Pos. Co, positive control; Neg. Co., negative control.

This article has been cited by other articles:

				R. Rizzo, M. Stignani, L. Melchiorri, and O. R. Baricordi Comment on "Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells" J. Immunol., April 15, 2009; 182(8): 4497 - 4497. [Full Text] [PDF]