| Autor: |
Hinrichs AC; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands., Kruize AA; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands., Lafeber FPJG; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands., Leavis HL; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands., van Roon JAG; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3508 Utrecht, The Netherlands. |
| Abstrakt: |
Primary Sjögren's syndrome (pSS) is an autoimmune disease characterised by B cell hyperactivity. CXCR5+ follicular helper T cells (Tfh), CXCR5-PD-1hi peripheral helper T cells (Tph) and CCR9+ Tfh-like cells have been implicated in driving B cell hyperactivity in pSS; however, their potential overlap has not been evaluated. Our aim was to study the overlap between the two CXCR5- cell subsets and to study their PD-1/ICOS expression compared to "true" CXCR5/PD-1/ICOS-expressing Tfh cells. CXCR5- Tph and CCR9+ Tfh-like cell populations from peripheral blood mononuclear cells of pSS patients and healthy controls (HC) were compared using flow cytometry. PD-1/ICOS expression from these cell subsets was compared to each other and to CXCR5+ Tfh cells, taking into account their differentiation status. CXCR5- Tph cells and CCR9+ Tfh-like cells, both in pSS patients and HC, showed limited overlap. PD-1/ICOS expression was higher in memory cells expressing CXCR5 or CCR9. However, the highest expression was found in CXCR5/CCR9 co-expressing T cells, which are enriched in the circulation of pSS patients. CXCR5- Tph and CCR9+ Tfh-like cells are two distinct cell populations that both are enriched in pSS patients and can drive B cell hyperactivity in pSS. The known upregulated expression of CCL25 and CXCL13, ligands of CCR9 and CXCR5, at pSS inflammatory sites suggests concerted action to facilitate the migration of CXCR5+CCR9+ T cells, which are characterised by the highest frequencies of PD-1/ICOS-positive cells. Hence, these co-expressing effector T cells may significantly contribute to the ongoing immune responses in pSS. |
