Direkt zum Inhalt
  1. Publizieren |
  2. Suche |
  3. Browsen |
  4. Neuzugänge rss |
  5. Open Access |
  6. Rechtsfragen |
  7. EnglishCookie löschen - von nun an wird die Spracheinstellung Ihres Browsers verwendet.

Immunosuppressive therapy influences the accelerated age-dependent T-helper cell differentiation in systemic lupus erythematosus remission patients

Schaier, Matthias ; Gottschalk, Claudius ; Uhlmann, Lorenz ; Speer, Claudius ; Kälble, Florian ; Eckstein, Volker ; Müller-Tidow, Carsten ; Meuer, Stefan ; Mahnke, Karsten ; Lorenz, Hanns-Martin ; Zeier, Martin ; Steinborn, Andrea

In: Arthritis Research & Therapy, 20 (2018), Nr. 278. S. 1-17. ISSN 1478-6362

[thumbnail of 13075_2018_Article_1778.pdf]
Vorschau
PDF, Englisch - Hauptdokument
Download (1MB) | Lizenz: Creative Commons LizenzvertragImmunosuppressive therapy influences the accelerated age-dependent T-helper cell differentiation in systemic lupus erythematosus remission patients von Schaier, Matthias ; Gottschalk, Claudius ; Uhlmann, Lorenz ; Speer, Claudius ; Kälble, Florian ; Eckstein, Volker ; Müller-Tidow, Carsten ; Meuer, Stefan ; Mahnke, Karsten ; Lorenz, Hanns-Martin ; Zeier, Martin ; Steinborn, Andrea steht unter einer Creative Commons Namensnennung 4.0

Zitieren von Dokumenten: Bitte verwenden Sie für Zitate nicht die URL in der Adresszeile Ihres Webbrowsers, sondern entweder die angegebene DOI, URN oder die persistente URL, deren langfristige Verfügbarkeit wir garantieren. [mehr ...]

Abstract

Background: CD4+ T cells are of great importance in the pathogenesis of systemic lupus erythematosus (SLE), as an imbalance between CD4+ regulatory T cells (Tregs) and CD4+ responder T cells (Tresps) causes flares of active disease in SLE patients. In this study, we aimed to find the role of aberrant Treg/Tresp cell differentiation for maintaining Treg/Tresp cell balance and Treg functionality.

Methods: To determine differences in the differentiation of Tregs/Tresps we calculated the percentages of CD45RA+CD31+ recent thymic emigrant (RTE) Tregs/Tresps and CD45RA+CD31− mature naive (MN) Tregs/Tresps, as well as CD45RA−CD31+ and CD45RA−CD31− memory Tregs/Tresps (CD31+ and CD31− memory Tregs/Tresps) within the total Treg/Tresp pool of 78 SLE remission patients compared with 94 healthy controls of different ages. The proliferation capacity of each Treg/Tresp subset was determined by staining the cells with anti-Ki67 monoclonal antibodies. Differences in the autologous or allogeneic Treg function between SLE remission patients and healthy controls were determined using suppression assays.

Results: With age, we found an increased differentiation of RTE Tregs via CD31+ memory Tregs and of RTE Tresps via MN Tresps into CD31− memory Tregs/Tresp in healthy volunteers. This opposite differentiation of RTE Tregs and Tresps was associated with an age-dependent increase in the suppressive activity of both naive and memory Tregs. SLE patients showed similar age-dependent Treg cell differentiation. However, in these patients RTE Tresps differentiated increasingly via CD31+ memory Tresps, whereby CD31− memory Tresps arose that were much more difficult to inhibit for Tregs than those that emerged through differentiation via MN Tresps. Consequently, the increase in the suppressive activity of Tregs with age could not be maintained in SLE patients. Testing the Tregs of healthy volunteers and SLE patients with autologous and nonautologous Tresps revealed that the significantly decreased Treg function in SLE patients was not exclusively attributed to an age-dependent diminished sensitivity of the Tresps for Treg suppression. The immunosuppressive therapy reduced the accelerated age-dependent Tresp cell proliferation to normal levels, but simultaneously inhibited Treg cell proliferation below normal levels.

Conclusions: Our data reveal that the currently used immunosuppressive therapy has a favorable effect on the differentiation and proliferation of Tresps but has a rather unfavorable effect on the proliferation of Tregs. Newer substances with more specific effects on the immune system would be desirable.

Dokumententyp: Artikel
Titel der Zeitschrift: Arthritis Research & Therapy
Band: 20
Nummer: 278
Verlag: BioMed Central
Ort der Veröffentlichung: London
Erstellungsdatum: 08 Feb. 2019 11:10
Erscheinungsjahr: 2018
ISSN: 1478-6362
Seitenbereich: S. 1-17
Institute/Einrichtungen: Medizinische Fakultät Heidelberg und Uniklinikum > Medizinische Universitäts-Klinik und Poliklinik
Medizinische Fakultät Heidelberg und Uniklinikum > Universitäts-Frauenklinik
Medizinische Fakultät Heidelberg und Uniklinikum > Universitäts-Hautklinik
Medizinische Fakultät Heidelberg und Uniklinikum > Institut für Immunologie
Medizinische Fakultät Heidelberg und Uniklinikum > Institut für Medizinische Biometrie
DDC-Sachgruppe: 610 Medizin
Freie Schlagwörter: Systemic lupus erythematosus, T-helper cell differentiation, Regulatory T cells, Proliferation capacity, Immunosuppressive therapy
Leitlinien | Häufige Fragen | Kontakt | Impressum |
OA-LogoDINI-Zertifikat 2013Logo der Open-Archives-Initiative