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Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen-driven T cell activation

Authors

  • I. Skrindo,

    1. Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway,
    2. ENT Department, Rikshospitalet, Oslo, Norway
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  • L. Farkas,

    1. Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway,
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  • E. O. Kvale,

    1. Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway,
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  • F.-E. Johansen,

    1. Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway,
    2. Division of Pathology, Rikshospitalet, Oslo, Norway
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  • F. L. Jahnsen

    1. Laboratory for Immunohistochemistry and Immunopathology, Centre for Immune Regulation, Institute of Pathology, University of Oslo, Oslo, Norway,
    2. Division of Pathology, Rikshospitalet, Oslo, Norway
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Correspondence:
Ingebjørg Skrindo, Institute of Pathology, University of Oslo and Division of Pathology, Rikshospitalet, Sognsvannsveien 20, N-0027 Oslo, Norway.
E-mail: ingebjorg.skrindo@rr-research.no

Summary

Background It has been suggested that allergic diseases are caused by defective suppression of allergen-specific Th2 cells by CD4+CD25+ regulatory T cells. However, such studies have been hampered by the difficulty in distinguishing regulatory T cells from CD25-expressing activated T cells. Recently, it was shown that conventional T cells expressed high levels of CD127, whereas regulatory T cells were CD127lo, allowing discrimination between these distinct T cell subpopulations.

Objective The aim of this study was to study whether the putative regulatory subset defined as CD4+CD25+CD127lo was involved in grass pollen-reactive T cell responses.

Methods Peripheral blood mononuclear cells (PBMCs) were obtained from allergic donors and non-atopic controls out of season. Grass pollen-induced cytokine production and proliferation were compared in cultures of undepleted cells and cells depleted of CD4+CD25+, CD4+CD25+CD127hi or CD4+CD25+CD127lo T cells.

Results Undepleted cell cultures from allergic patients showed significantly increased proliferation and Th2 cytokine production compared with non-atopic controls. Depletion of all CD25+ T cells did not increase cytokine production or proliferation, and more importantly, no increase in Th2 cytokine production or proliferation was observed in cell cultures depleted of CD4+CD25+CD127lo cells (putative regulatory T cells) compared with undepleted PBMCs in both the allergic and the non-atopic group.

Conclusion Our study showed that T cells from grass pollen-allergic patients and non-atopic controls responded very differently to grass pollen extract, but this difference could not be explained by differences in regulatory T cell function. Further studies are needed to understand the importance of regulatory T cells in allergy.

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