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 Google Scholar Google Scholar Articles by Kang, Y. Articles by Zheng, G. Search for Related Content PubMed PubMed Citation Articles by Kang, Y. Articles by Zheng, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DEXAMETHASONE

Cutting Edge: Immunosuppressant as Adjuvant for Tolerogenic Immunization¹

Youmin Kang^2,*,, Lipeng Xu^2,*, Bin Wang, Aoshuang Chen^3,* and Guoxing Zheng^3,*

^* Department of Biomedical Sciences, University of Illinois College of Medicine, Rockford, Illinois 61107; and State Key Laboratories for Agro-Biotechnology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, China

Vaccination for autoimmune and alloimmune diseases has long been an attractive idea. Yet, there is no suitable adjuvant to forcefully steer the immune response toward tolerance. In this study we show that dexamethasone, a potent glucocorticoid immunosuppressant, can function as a tolerogenic adjuvant when applied together with peptide immunogen. BALB/c mice with pre-established delayed-type hypersensitivity to hen OVA were immunized with an OVA-derived, MHC II-restricted peptide (OVA_323–339) in the presence of dexamethasone. The treatment caused long-term desensitization in treated animals to hen OVA via a dexamethasone-dependent tolerogenic mechanism that blocks maturation of dendritic cells and expands OVA_323–339-specific CD4⁺CD25⁺Foxp3⁺ regulatory T cells in vivo. Similar treatment of NOD mice using dexamethasone and an insulin-derived, MHC II-restricted peptide (B:9–23) prevented predisposed spontaneous diabetes. Remarkably, in both models, dexamethasone-augmented immunization induced long-term persistent, Ag-specific regulatory T cells responsive to recall Ags. These results reveal for the first time the potential usefulness of immunosuppressants as tolerogenic adjuvants.

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 National Institutes of Health Grant RO1CA92243 (to A.C.) and by a grant from the Illinois Department of Public Health (to G. Z.). Y.K. was a recipient of a scholarship from the China Scholarship Council.

² Y.K. and L.X. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Aoshuang Chen or Dr. Guoxing Zheng, Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Rockford, IL 61107. E-mail addresses: aoshuang{at}uic.edu and guoxingz{at}uic.edu

⁴ Abbreviations used in this paper: DEX, dexamethasone; DC, dendritic cell; DTH, delayed-type hypersensitivity; LN, lymph node; Teff, effector T cell; Treg, regulatory T cell.