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Processing-dependent and -independent pathways for recognition of iodinated contrast media by specific human T cells

Authors

  • M. Keller,

    1. Adverse Drug Reactions – Analysis and Consulting (ADR-AC) GmbH, Bern, Switzerland
    2. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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    • *M.K. and M.L. contributed equally to this work.

  • M. Lerch,

    1. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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    • *M.K. and M.L. contributed equally to this work.

    • Current address: Dermatology/Allergology, Kantonsspital, St. Gallen, Switzerland.

  • M. Britschgi,

    1. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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  • V. Tâche,

    1. Adverse Drug Reactions – Analysis and Consulting (ADR-AC) GmbH, Bern, Switzerland
    2. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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  • B. O. Gerber,

    1. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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  • M. Lüthi,

    1. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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  • P. Lochmatter,

    1. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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  • G. Kanny,

    1. EA 3999 ‘Allergic diseases: diagnosis and therapeutics’, Department of Internal Medicine, Clinical Immunology and Allergology, University Hospital, Nancy Cedex, France
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  • A. J. Bircher,

    1. Allergy Unit, Department of Dermatology, University Hospital, Basel, Switzerland
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  • C. Christiansen,

    1. Research and Development, GE Healthcare, Oslo, Norway
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  • W. J. Pichler

    1. Adverse Drug Reactions – Analysis and Consulting (ADR-AC) GmbH, Bern, Switzerland
    2. Department of Rheumatology, Clinical Immunology, and Allergology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
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Correspondence:
Werner J. Pichler, University Clinic for Rheumatology and clinical Immunology/Allergology, PKT2 D572, Inselspital, CH-3010 Bern, Switzerland. E-mail: werner.pichler@insel.ch

Summary

Background One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) show a broad range of cross-reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far.

Objective To determine how T cells specifically recognize CM.

Methods CM-specific TCCs were generated from human blood of three CM-allergic patients and a specific TCR was transfected into a mouse T cell hybridoma. Functional analysis such as proliferation assays, IL-2 secretion assays, and calcium influx experiments were performed using irradiated, glutaraldehyde-fixed, CM-pre-incubated, human leucocyte antigen (HLA)-DR-matched or -mismatched antigen-presenting cells (APCs), and HLA-blocking antibodies.

Results We identified two mechanisms of T cell stimulation: some TCCs and the transfectant reacted to CM independent of uptake by APCs because proliferation/IL-2 secretion occurred in the presence of glutaraldehyde-fixed APCs, and intracellular calcium increased within seconds after drug addition. Other TCCs required functional APCs, compatible with uptake and presentation of CM on MHC-class II molecules, as implied by three findings: (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be washed away from CM-pre-incubated APCs; and (3) the optimal pulsing time was 10–20 h. Because allogeneic, MHC-matched, CM-pulsed APCs could induce proliferative responses as well, the ability of CM uptake and presentation is not unique to APCs from patients with CM-induced delayed hypersensitivity.

Conclusion Our data suggest that CM may be stimulatory for T cells either by direct binding to the MHC–TCR complex or by binding after uptake and processing by APCs. This questions the assumed inert nature of CM.

Cite this as: M. Keller, M. Lerch, M. Britschgi, V. Tâche, B. O. Gerber, M. Lüthiuthi, P. Lochmatter, G. Kanny, A. J. Bircher, C. Christiansen and W. J. Pichler, Clinical & Experimental Allergy, 2010 (40) 257–268.

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