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Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis

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Cell Stress and Chaperones Aims and scope

Abstract

Heat shock protein 60 (hsp60) is a highly conserved stress protein and target of self-reactive T cells in various inflammatory diseases. Not much is known about a possible role in atopic disease. As atopic diseases are considered to be the result of a disturbance in the balance between T helper cells type 2 and regulatory T cells, it is of interest to know whether hsp60 acts as a bystander antigen in atopic disease. Our aim was to investigate whether hsp60 is involved in the chronicity of inflammation of atopic dermatitis (AD). We studied the expression of hsp60 in skin tissue of adults with AD by immunohistochemistry. Peripheral blood mononuclear cells (PBMC) of children with AD were cultured with hsp60 and proliferative responses, cytokine secretion, surface markers, and functional assays were compared to responses of PBMC of healthy controls (HC). Hsp60 was detected more in lesional skin of AD patients compared to nonlesional skin. Furthermore, PBMC of children with AD proliferated more strongly in response to hsp60 compared to HC. hsp60-reactive T cells of atopic children produced high levels of IFNγ and low levels of IL-10. In vitro activation with hsp60 leads to the induction of CD4+CD25bright T cells expressing FOXP3 in both HC as well as in atopic children. However, despite their regulatory phenotype, hsp60-induced CD4+CD25brightCD127−FOXP3+ T cells of AD patients were incapable of suppressing effector T cells in vitro. hsp60 is recognized by proinflammatory (IFNγ high, IL-10 low) T cells in atopic patients and is more present in lesional AD skin. This suggests that hsp60-specific T cell responses contribute to local inflammation in AD.

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Abbreviations

TH2:

T helper cells type 2

TH1:

T helper cells type 1

Tregs :

Naturally occurring or induced CD4+CD25+FOXP3+ regulatory T cells

hsp:

Heat shock protein(s)

hsp60:

Human heat shock protein 60

PBMC:

Peripheral blood mononuclear cells

AD:

Atopic dermatitis

FACS:

Fluorescence-activated cell sorting

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Authors and Affiliations

  1. Department of General Paediatrics, Wilhelmina Children’s Hospital, Utrecht, Netherlands

    Berber Kapitein, Joost A. Aalberse & Maarten O. Hoekstra

  2. Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children’s Hospital, KC 01.069.0, P.O. Box 85090, 3508 AB, Utrecht, Netherlands

    Berber Kapitein, Joost A. Aalberse, Mark R. Klein, Wilco de Jager & Berent J. Prakken

  3. Department of Dermatology, University Medical Centre Utrecht, Utrecht, The Netherlands

    Edward F. Knol

  4. Pediatric Intensive Care Unit, Sophia Children’s Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands

    Berber Kapitein

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  1. Berber Kapitein
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Correspondence to Berent J. Prakken.

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Supplementary Figure 1

Protein-induced T cell proliferation in atopic children and healthy controls. PBMCs were cultured for 96 hours in the presence of ConA. Boxes show IQR for each group of data, horizontal lines show the median. Light grey boxes = healthy controls, dark grey boxes = atopic children. SI is indicated on a logarithmic scale. The difference in SI between the HC and atopic children was not significant (p = 0.1) after stimulation with ConA (JPEG 19 kb)

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Kapitein, B., Aalberse, J.A., Klein, M.R. et al. Recognition of self-heat shock protein 60 by T cells from patients with atopic dermatitis. Cell Stress and Chaperones 18, 87–95 (2013). https://doi.org/10.1007/s12192-012-0361-3

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  • DOI: https://doi.org/10.1007/s12192-012-0361-3

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