Lymphopenia in primary Sjögren's syndrome is associated with premature aging of naïve CD4+ T cells. (30th March 2020)

• Record Type: Journal Article
• Authors: Fessler, Johannes; Fasching, Patrizia; Raicht, Andrea; Hammerl, Sabrina; Weber, Jennifer; Lackner, Angelika; Hermann, Josef; Dejaco, Christian; Graninger, Winfried B; Schwinger, Wolfgang; Stradner, Martin H
• Is Part Of: Rheumatology. Volume 60:Number 2(2021)
• Page Start: 588
• Page End: 597
• Publication Date: 2020-03-30
• Subjects: T cells -- Sjögren syndrome -- inflammation -- autoimmunity; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/keaa105
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objective: To investigate peripheral lymphopenia, a frequent finding in primary Sjögren's syndrome (pSS) associated with higher disease activity and increased mortality. Methods: 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). Results: 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. Conclusion: 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.