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Deutscher Rheumatologiekongress 2023

51. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh)
37. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)
33. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

30.08. - 02.09.2023, Leipzig

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Recovery of regulatory T cells by in vitro stimulation with low doses of interleukin-2 in patients with myositis

Meeting Abstract

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  • Justus Ohmes - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Sara Comdühr - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Luisa Monne - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Finn Gerlach - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Antje Müller - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Reza Akbarzadeh - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck; Department of Rheumatology and Clinical Immunology, Lübeck
  • Gabriela Riemekasten - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck
  • Jens Humrich - Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie, Lübeck

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. Deutscher Rheumatologiekongress 2023, 51. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 37. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 33. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Leipzig, 30.08.-02.09.2023. Düsseldorf: German Medical Science GMS Publishing House; 2023. DocET.25

doi: 10.3205/23dgrh044, urn:nbn:de:0183-23dgrh0441

Veröffentlicht: 30. August 2023

© 2023 Ohmes et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Introduction: In previous works we found that patients with polymyositis/dermatomyositis (PM/DM) exhibit a loss of the CD25+ regulatory T cell (Treg) subset [1] suggesting a deficiency of the Treg growth and survival factor interleukin-2 (IL-2) similar to patients with SLE for which low-dose IL-2 therapy has been successfully translated into clinical studies in recent years [2], [3], [4]. As a prerequisite for an IL-2 based immunotherapy of PM/DM, we investigated whether CD25 expression in Treg can be restored by in vitro stimulation with low doses of IL-2 and whether this leads to an increased transcription of molecules that are associated with the suppressive function of Treg.

Methods: Peripheral blood mononuclear cells (PBMC) from patients with PM/DM (n=6–8) were stimulated in vitro for 24 hours with low (1 ng/ml), mid (5 ng/ml) or high doses (10 ng/ml) of recombinant human IL-2. Expression of CD25 in CD4+FoxP3+CD127lo Treg and conventional CD4+FoxP3- T cells and changes in the frequencies of CD25-expressing Treg subsets were quantified by flow cytometry using QuantiBRITE® beads. mRNA expression of the IL-2 receptor chains CD25, CD122 and CD132 and of Helios, CD152, CD39 and IL-10 was quantified in PBMC by RT-PCR.

Results: Stimulation with the lowest dose of IL-2 selectively increased the frequencies of the CD25+ Treg subsets and led to an increase in the amount of CD25 surface molecules per cell, which was not further augmented when high doses of IL-2 were tested. Stimulation with the lowest dose of IL-2 also increased mRNA expression of all three IL-2 receptor chains (CD25, CD122, CD132) and of Helios, CD152, CD39 and IL-10. In contrast to the analyses at a protein level, increases in CD25 mRNA, and also of the other tested molecules, were mostly pronounced with the highest dose of IL-2, suggesting a differential regulation of protein expression and mRNA transcription.

Conclusion: Stimulation with low doses of IL-2 is capable to recover Treg activity and to induce a favorable immunoregulatory expression pattern in PBMC from patients with PM/DM. The reversibility of these Treg defects provides an important rationale for the clinical translation of low-dose IL-2 therapy in DM/PM.

Gliederung

References

1.
Monne LR, Comdühr S, Gerlach F, Müller A, Riemekasten G, Humrich JY. IL-2 deprived phenotype of FoxP3+regulatory T cells and phenotypic alterations of conventional CD4+ T cells in patients with inflammatory myopathies and primary Sjogren's syndrome. Ann Rheum Dis 2022;81(Suppl 1):1148-9. Meeting Abstract AB0028.
2.
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4.
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