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The Journal of Immunology, 2008, 181, 8096 -8102
Copyright © 2008 by The American Association of Immunologists, Inc.

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Promiscuous Interaction between Gold-Specific T Cells and APCs in Gold Allergy1

Hideo Hashizume2, Naohiro Seo, Taisuke Ito, Masahiro Takigawa and Hiroaki Yagi

Department of Dermatology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan

Gold compounds clinically used as immunomodulators have high potential to evoke hypersensitivity reactions as an adverse effect. To explore the mechanism of gold allergy, we immunologically characterized T cells infiltrating skin rashes and generated 44 gold-specific T cell clones and lines from a rheumatoid arthritis patient who developed skin rashes and systemic symptoms after gold treatment. CD4+ and CD8+ cells predominantly infiltrating the skin rashes and some of the T cell clones and lines shared common Vβs. These cells exhibited Th0-like, Th2-like, and Tc1-like cytokine profiles, and showed chemotactic activities for thymus and activation-regulated chemokine and IFN-{gamma}-inducible protein-10 corresponding to the cytokine profiles. T cell recognition of gold consisted of MHC-restricted and MHC-independent pathways. Blocking studies with anti-MHC Abs indicated that the groove of MHC in APCs, where Ags should ordinarily be settled, did not serve as a conjugating site of gold for these T cells in certain cases. These observations raise the possibility that gold-specific CD4+ and CD8+ T cells and APCs promiscuously interact under stimulation with gold, resulting in various clinical manifestations in gold allergy.

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 partly supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17591168).

2 Address correspondence and reprint requests to Dr. Hideo Hashizume, Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192, Japan. E-mail address: hihashiz{at}hama-med.ac.jp

3 Abbreviations used in this paper: RA, rheumatoid arthritis; CBA, cytometric bead array; FCM, flow cytometry; IP-10, IFN-{gamma}-inducible protein-10; LCL, lymphoblastoid B cell line; TARC, thymus and activation-regulated chemokine; TCC, T cell clone; TCL, T cell line.

4 The online version of this article contains supplemental material.







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