Artikel
CD4+CD8+ double-positive T-cells display both memory cell and innate features in granulomatosis with polyangiitis
Suche in Medline nach
Autoren
-
Anja Kerstein
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
-
Silke Schüler
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
-
Silke Pitann
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
-
Sebastian Klapa
- Institut für experimentelle Medizin, Sektion Maritime Medizin der Christian-Albrechts-Universität zu Kiel und Klinik für Rheumatologie und klinische Immunologie Universitätsklinikum Schleswig-Holstein Campus Lübeck, Kronshagen
-
Antje Müller
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
-
Gabriela Riemekasten
- Universität zu Lübeck, Klinik für Rheumatologie und Klinische Immunologie, Lübeck
-
Peter Lamprecht
- Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
| Veröffentlicht: | 4. September 2017 |
|---|
Gliederung
Text
Background: Circulating and lesional CD4+CD8+ double-positive (DP) T-cells have been linked to infectious diseases, cancer, and autoimmune diseases. However, a general consensus regarding their origin and function is still missing. In granulomatosis with polyangiitis (GPA), we found increased frequencies of circulating DP T-cells. Here we present further details of the phenotypic characterization of DP T-cells in GPA.
Methods: Peripheral blood mononuclear cells were freshly isolated from blood of GPA patients and healthy controls (HC) (n=20 each). Phenotypic characterization was carried out by extra- and intracellular staining using antibodies directed against surface markers (CD3, CD4, CD8, CD24, CD28, CD45RA, NKG2D, CCR4, CCR6, CCR7) and intracellular markers (IFNy, IL4, IL17, IL22, terminal deoxynucleotidyl transferase (tdt)) and subsequent flow cytometric analysis.
Results: In GPA, the percentage of circulating DP T-cells was higher in remission than during active disease. We have previously shown that the majority of DP T-cells display a memory cell phenotype with co-expression of the co-stimulatory molecule CD28 and NK-receptor NKG2D, both in GPA and HC. Here we show that up to 50% of DP T-cells express the activation markers and chemokine receptors CCR4 and CCR6. In contrast, expression of markers of thymic origin, i.e. CD24 and tdt, were lacking. Analysis of intracellular cytokine expression in DP T-cells showed a predominance of Th1-type and Th17 cytokine production in GPA compared to HC.
Conclusion: In GPA, the majority of DP T-cells display markers of memory cell phenotype and function (Th1/Th17), innate features (NKG2D), and activation and migratory potential (CCR4, CCR6). Lack of CD24 and tdt expression is in line with earlier studies suggesting an extrathymic origin of circulating DP T-cells from CD4+ and CD8+ single-positive memory T-cells re-expressing the other co-receptor rather than a recent thymic origin of DP T-cells. Altogether, DP T-cells represent a distinct pro-inflammatory T-cell population potentially contributing to chronic inflammation and autoimmunity in GPA.
