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Analysis of FOXP3+ regulatory T cell subpopulations in peripheral blood and tissue of patients with systemic lupus erythematosus

  • Novel Aspects in Lupus, 2017
  • Published:
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Abstract

Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4+ T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry. CD4+ and FOXP3+ T cells in skin and kidney biopsies of patients with SLE were quantified by immunohistochemistry. CD4+CD25+/++FOXP3+ and CD4+CD25+CD45RA−/CD45RO+ T cell frequencies were significantly higher in PB from patients with active compared to inactive SLE. The fraction of CD4+CD25++FOXP3+ Tregs and CD4+CD25+CD45RA+/CD45RO− naïve Tregs was not significantly different between these groups. CD4+CD25++ Tregs from active SLE patients comprised significantly less CD27+ cells and more CCR6+ cells compared to patients with inactive SLE. The percentage of CD4+FOXP3+ T cells among inflammatory infiltrates in skin and kidney biopsies of SLE patients was not different from other inflammatory skin/kidney diseases. In conclusion, although CD4+FOXP3+ T cell frequencies in the inflamed tissues of SLE patients were comparable to other inflammatory diseases, distinct T cell subpopulations appeared misbalanced in PB of patients with active SLE. Here, cells phenotypically resembling activated T cells, but not Tregs, were increased compared to patients with inactive SLE. Within Tregs of patients with active SLE, markers related to Treg function and homing were altered.

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Acknowledgements

We thank Astrid Riehl, Christine Stumpf, Raphael Klembt, and Sabine Herzog, former members of the Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center Heidelberg, Germany, for their support in the FACS analysis, help in immunohistochemistry, and for support in the preparation of the manuscript, respectively. We are also indebted to Professor Martin Glombitza, MD, Municipal Hospital Karlsruhe, Department of Nephrology and Rheumatology, for providing us with blood samples of patients with SLE, and Dr. Ferdinand Toberer, MD, Professor Wolfgang Hartschuh, MD, and Professor Alexander Enk, MD, University of Heidelberg, Department of Dermatology, for providing us with skin biopsies of patients with SLE. We also thank Aysche Landmann, Division of Immunogenetics, Tumor Immunology Program, German Cancer Research Center Heidelberg, Germany, for copy-editing the manuscript.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Angelika Schmidt & Szabolcs Éliás

    Present address: Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, & Science for Life Laboratory, Stockholm, Sweden

  2. Cosima C. Rieger

    Present address: Roche Diabetes Care GmbH, Global Medical & Scientific Affairs, Mannheim, Germany

  3. Ram Kumar Venigalla

    Present address: Babraham Institute, Cambridge, UK

Authors and Affiliations

  1. Division of Immunogenetics (D030), Tumor Immunology Program, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Angelika Schmidt, Cosima C. Rieger, Peter H. Krammer & Annegret Kuhn

  2. Internal Medicine V, Division of Rheumatology, University of Heidelberg, Heidelberg, Germany

    Ram Kumar Venigalla, Regina Max & Hanns-Martin Lorenz

  3. Department of Cellular and Molecular Pathology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Hermann-Josef Gröne

  4. Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center Mainz, Mainz, Germany

    Annegret Kuhn

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Correspondence to Annegret Kuhn.

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The study was approved by the local ethics committee of the University of Heidelberg, Heidelberg, Germany, and was conducted according to the Declaration of Helsinki.

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Angelika Schmidt and Cosima C. Rieger are shared first authors.

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Schmidt, A., Rieger, C.C., Venigalla, R.K. et al. Analysis of FOXP3+ regulatory T cell subpopulations in peripheral blood and tissue of patients with systemic lupus erythematosus. Immunol Res 65, 551–563 (2017). https://doi.org/10.1007/s12026-017-8904-4

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