Article
Loss of the CD25+ regulatory T cell subset in inflammatory myopathies and primary Sjogren’s syndrome
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Authors
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Luisa R. Monne
- University Hospital Schleswig-Holstein - Campus Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck
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Sara Comdühr
- University Hospital Schleswig-Holstein - Campus Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck
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Antje Müller
- University Hospital Schleswig-Holstein - Campus Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck
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Gabriela Riemekasten
- University Hospital Schleswig-Holstein - Campus Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck
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Jens Y. Humrich
- University Hospital Schleswig-Holstein - Campus Lübeck, Department of Rheumatology and Clinical Immunology, Lübeck
| Published: | September 9, 2020 |
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Outline
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Introduction: A defect in regulatory T cell (Treg) homeostasis due to an acquired deficiency of interleukin-2 (IL-2) plays an important role in the pathogenesis of systemic lupus erythematosus (SLE) [1], [2]. However, it is still unclear whether a defect in the Treg-IL-2 axis is also involved in other connective tissue diseases such as inflammatory myopathies or primary Sjogren´s syndrome (pSS).
The aim of our study was to analyze Treg and conventional CD4+ T cell (Tcon) subsets of patients with poly- and dermatomyositis (PM/DM) and pSS for typical features of IL-2 deficiency in comparison to healthy controls (HC).
Methods: PBMC were isolated from patients with PM/DM (n=20), pSS (n=8) and age- and sex-matched HC (n=13) using gradient density centrifugation. Different T-cell subpopulations were analyzed using multicolor flow cytometry. Statistical analysis was done by Mann-Whitney test.
Results: Frequencies of FoxP3+CD127lo Treg among CD3+CD4+T cells were higher in pSS patients compared to PM/DM (p<0.01) and, less pronounced, compared to HC (p=0.081), while there was a moderate decrease in PM/DM patients compared to HC (p=0.057). However, significantly lower frequencies of CD25+ cells among Treg were observed in both PM/DM and pSS patients compared to HC (PM/DM: p<0.001, pSS: p<0.05). In parallel we observed a shift in the distribution of Tcon subsets in pSS patients characterized by lower frequencies of CD45RO-CCR7+ naïve and higher frequencies of CD45RO+CCR7- effector/memory cells among CD3+CD4+FoxP3- Tcon compared to HC (p<0.05 and p<0.05) and PM/DM patients (p<0.001 and p<0.001).
Conclusion: The loss of the CD25+ Treg subset in PM/DM and pSS patients is similar to previous findings in SLE patients1 and suggests an insufficient availability for IL-2. The different distribution of total Treg and of Tcon subsets between pSS and PM/DM patients might reflect differences in both the activation status of Treg/Tcon and the regulation of Tcon responses in these diseases.
Disclosures: Nothing to disclose
References
- 1.
- von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus. Ann Rheum Dis. 2016;75(7):1407-15. DOI: 10.1136/annrheumdis-2015-207776
- 2.
- Humrich JY, von Spee-Mayer C, Siegert E, et al. Low-dose interleukin-2 therapy in refractory systemic lupus erythematosus: an investigator-initiated, single-centre phase 1 and 2a clinical trial. Lancet Rheumatol. 2019; 1(1):e44-e54. DOI: 10.1016/S2665-9913(19)30018-9
