The onset of active disease in systemic lupus erythematosus patients is characterised by excessive regulatory CD4+-T-cell differentiation

• Verfasst von: Schaier, Matthias [VerfasserIn]
• Verfasst von: Gottschalk, Claudius [VerfasserIn]
• Verfasst von: Kälble, Florian [VerfasserIn]
• Verfasst von: Uhlmann, Lorenz [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Meuer, Stefan [VerfasserIn]
• Verfasst von: Mahnke, Karsten [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Zeier, Martin [VerfasserIn]
• Verfasst von: Steinborn-Kröhl, Andrea [VerfasserIn]
• Titel: The onset of active disease in systemic lupus erythematosus patients is characterised by excessive regulatory CD4+-T-cell differentiation
• Verf.angabe: M. Schaier, C. Gottschalk, F. Kälble, L. Uhlmann, V. Eckstein, C. Müller-Tidow, S. Meuer, K. Mahnke, H.-M. Lorenz, M. Zeier, A. Steinborn
• E-Jahr: 2021
• Jahr: 09/04/2021
• Umfang: 10 S.
• Fussnoten: Im Titel ist "+" hochgestellt ; Gesehen am 15.07.2021
• Titel Quelle: Enthalten in: Clinical and experimental rheumatology
• Ort Quelle: Pisa : [Verlag nicht ermittelbar], 1999
• Jahr Quelle: 2021
• Band/Heft Quelle: 39(2021), 2, Seite 279-288
• ISSN Quelle: 1593-098X
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CD4-Positive T-Lymphocytes
• Sach-SW: Cell Differentiation
• Sach-SW: Humans
• Sach-SW: Lupus Erythematosus, Systemic
• Sach-SW: Lymphocyte Activation
• Sach-SW: T-Lymphocyte Subsets
• Sach-SW: T-Lymphocytes, Regulatory
• K10plus-PPN: 1762956756

Abstract

OBJECTIVES: An imbalance between CD4+-regulatory T-cells (Tregs) and CD4+-responder T-cells (Tresps) correlates with active disease flares in systemic lupus erythematosus (SLE) patients. Both cell subsets consist of highly proliferating Tregs/Tresps expressing inducible T-cell co-stimulatory molecule (ICOS) and less proliferating ICOS--Tregs/Tresps. METHODS: Six-colour-flow-cytometric analysis was used to examine the effect of ICOS+- and ICOS--Treg/Tresp cell differentiation on the composition of the total CD4+-T-helper cell pool with ICOS+- and ICOS--Tregs/Tresps. Functionality of Tregs was examined using suppression assays. RESULTS: In 83 healthy volunteers, the ratio of ICOS+-Tregs/ICOS+-Tresps increased significantly with age, while that of ICOS--Tregs/ICOS--Tresps did not change. In 86 SLE patients (SLEDAI <7), disease activity was associated with an age-independently increased ratio of both ICOS+-Tregs/ICOS+-Tresps and ICOS--Tregs/ICOS--Tresps. In these patients, the functional activity of ICOS+-Tregs, but not of ICOS--Tregs, was preserved. In 13 markedly active disease patients (SLEDAI >7), the percentage of both ICOS+-Tregs and ICOS+-Tresps, was strongly increased within total CD4+-T-helper cells. However, the increased ratio of ICOS+-Tregs/ICOS+-Tresps was not maintained in these patients, due to terminal differentiation and accumulation of naïve cells within total ICOS+-Tregs. Despite increased differentiation of both ICOS--Tregs and ICOS--Tresps, the percentage of ICOS--Tregs increased within CD4+-T-helper cells, while that of ICOS--Tresps decreased, resulting in a significantly increased ratio of ICOS--Tregs/ICOS--Tresps independent of age. CONCLUSIONS: Our data reveal a crucial role of Treg immune senescence for the occurrence of disease flares in SLE patients, with ICOS+-Treg cells being most affected.