Antigen dose-dependent suppression of murine IgE responses is mediated by CD4CD8 double-negative T cells

Authors

  • C. Barwig,

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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  • V. Raker,

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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  • E. Montermann,

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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  • S. Grabbe,

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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  • A. B. Reske-Kunz,

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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  • S. Sudowe

    1. The Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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Correspondence:
Dr Stephan Sudowe, Clinical Research Unit Allergology, Department of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Str. 63, D-55131 Mainz, Germany.
E-mail: sudowe@mail.uni-mainz.de

Summary

Background The IgE response against protein antigens is profoundly influenced by the dose used for sensitization.

Objective The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation.

Methods Wild-type mice as well as T helper (Th)1-deficient IL-12p40−/− and IFN-γ−/− mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets among splenocytes from K01 and K100 mice was compared using fluorocytometry and RT-PCR analysis. Splenocytes or T cell subpopulations were transferred into naïve mice and the effect of lymphocyte transfer on IgE production after priming of recipients with low antigen doses was determined.

Results Specific IgE production was considerably impaired in K100 mice. Antigenic restimulation revealed hypoproliferation of K100 splenocytes and reduced production of Th2 cytokines IL-4, IL-5 and IL-13, but no induction of IFN-γ production. Moreover, lymphocytes from K01 and K100 mice did not show significant differences in the expression of molecules associated with the phenotype or activity of conventional regulatory T cells. Transfer of splenocytes or purified T cells from K100 mice substantially suppressed the induction of IgE production in the recipients in an antigen- and isotype-specific manner. Neither CD4+ nor CD8+ T cells from K100 mice were able to inhibit IgE formation; instead, we identified CD4CD8 double-negative T cells (dnT cells) as the principal T cell population, which potently suppressed IgE production.

Conclusion Our data demonstrate that CD4CD8 dnT cells play a major role in the regulation of IgE responses induced by high antigen doses.

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