Lymphopenia in primary Sjögren's syndrome is associated with premature aging of naïve CD4+ T cells.
Rheumatology (Oxford)
; 60(2): 588-597, 2021 02 01.
Article
em En
| MEDLINE
| ID: mdl-32227243
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 ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Síndrome de Sjogren
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Subpopulações de Linfócitos T
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Senilidade Prematura
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Linfopenia
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prevalence_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Rheumatology (Oxford)
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Áustria