Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Fessler, J; Fasching, P; Raicht, A; Hammerl, S; Weber, J; Lackner, A; Hermann, J; Dejaco, C; Graninger, WB; Schwinger, W; Stradner, MH.
Lymphopenia in primary Sjögren's syndrome is associated with premature aging of naïve CD4+ T cells.
Rheumatology (Oxford). 2021; 60(2):588-597
Doi: 10.1093/rheumatology/keaa105
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PubMed
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- Führende Autor*innen der Med Uni Graz
- Fessler Johannes
- Schwinger Wolfgang
- Co-Autor*innen der Med Uni Graz
- Dejaco Christian
- Fasching Patrizia
- Graninger Winfried
- Hermann Josef
- Lackner Angelika
- Stradner Martin Helmut
- Weber Jennifer
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- Abstract:
- To investigate peripheral lymphopenia, a frequent finding in primary Sjögren's syndrome (pSS) associated with higher disease activity and increased mortality. Prospective, cross-sectional study of consecutive patients with pSS (n = 66) and healthy controls (n = 181). Lymphocyte subsets were analysed by flow cytometry, naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells were purified by MACS technology. In vitro proliferation and senescence-associated β-galactosidase (SABG) were assessed by flow cytometry. Telomere length and TCR excision circles (TREC) were measured by real-time PCR. Telomerase activity was analysed according to the telomeric repeat amplification protocols (TRAP). In pSS, lymphopenia mainly affected naïve CD4+ T cells. We noted a lower frequency of proliferating naïve CD4+ T cells ex vivo and decreased homeostatic proliferation in response to IL-7 stimulation in vitro. Furthermore, naïve CD4+ T cells exhibited signs of immune cell aging including shortened telomeres, a reduction in IL-7R expression and accumulation of SABG. The senescent phenotype could be explained by telomerase insufficiency and drastically reduced levels of T-cell receptor excision circles (TRECs), indicating a history of extensive post-thymic cell division. TRECs correlated with the number of naïve CD4+ T cells linking the extend of earlier proliferation to the inability to sustain normal cell numbers. In pSS, evidence for increased proliferation of naïve CD4+ T cells earlier in life is associated with a senescent phenotype unable to sustain homeostasis. The lack of naïve CD4+ T cells forms the basis of lymphopenia frequently observed in pSS. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
- Find related publications in this database (Keywords)
- T cells
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