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Langerhans Cells Suppress Contact Hypersensitivity Responses Via Cognate CD4 Interaction and Langerhans Cell-Derived IL-10¹

Botond Z. Igyarto,^* Matthew C. Jenison,^* Jan C. Dudda,^¶ Axel Roers, Werner Müller, Pandelakis A. Koni, Daniel J. Campbell,^¶ Mark J. Shlomchik,^|| and Daniel H. Kaplan^2*

^*Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455; Institute of Immunology, TU-Dresden, Dresden, Germany; University of Manchester, Manchester, U.K.; Molecular Immunology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA, 30912; ^¶Benaroya Research Institute, Seattle, WA 98195 and Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195; and ^||Departments of Laboratory Medicine and Immunobiology, Yale University, New Haven, CT 06520

Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of T regulatory cells. CHS responses and Ag-specific T cells are increased in mice in which MHC class II is ablated specifically in LC suggesting that direct cognate interaction between LC and CD4 cells is required for suppression. LC-derived IL-10 is also required for optimal inhibition of CHS. Both LC-derived IL-10-mediated suppression and full LC activation require LC expression of MHC class II. These data support a model in which cognate interaction of LC with CD4 T cells enables LC to inhibit expansion of Ag-specific responses via elaboration of IL-10.

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 NIH R01-AR056632 (to D.H.K.) and R01-AR44077 (to M.J.S.).

² Address correspondence and reprint requests to Dr. Daniel H. Kaplan, Department of Dermatology/Center for Immunology, 6-118 NHH, 312 Church Street SE, Minneapolis, MN 55455. E-mail address: dankaplan{at}umn.edu

³ Abbreviations used in this paper: LC, Langerhans cell; CHS, contact hypersensitivity; DT, diphtheria toxin; DTA, active subunit of diphtheria toxin; DNFB, 2,4-dinitro-fluorobenzene; DNBS, 2,4-dinitrobenzenesulfonic acid; WT, wild type; MHC-II, MHC class II; DC, dendritic cell; LN, lymph node; dDC, dermal DC; Treg, regulatory T cell.

⁴ The online version of this article contains supplemental material.