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Front Immunol. 2018 Feb 1;9:95. doi: 10.3389/fimmu.2018.00095. eCollection 2018.

Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis.

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Department of Rheumatology and Immunology, Medical University of Graz, Graz, Austria.
Department of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
Department of Internal Medicine VI, Innsbruck Medical University, Innsbruck, Austria.
Rheumatology Service, South Tyrolean Health Trust, Hospital Bruneck, Bruneck, Italy.



T-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid arthritis (RA). Premature senescence of lymphocytes including the accumulation of senescent CD4+ T-cells is a hallmark feature of RA. Whether T-cell senescence is associated with bone loss in RA patients is elusive so far.


This includes a prospective study of consecutive patients with RA (n = 107), patients with primary osteopenia/-porosis (n = 75), and healthy individuals (n = 38). Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry scan. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed to analyze the pro-osteoclastic phenotype and the function of senescent CD4+CD28- T-cells.


Patients with osteopenia/-porosis yielded a higher prevalence of senescent CD4+CD28- T-cells than individuals with normal BMD, in the RA, as well as in the non-RA cohort. Receptor activator of nuclear factor kappa-B ligand (RANKL) was expressed at higher levels on CD4+CD28- T-cells as compared to CD28+ T-cells. Stimulation with interleukin-15 led to an up-regulation of RANKL expression, particularly on CD28- T-cells. CD4+CD28- T-cells induced osteoclastogenesis more efficiently than CD28+ T-cells.


Our data indicate that senescent T-cells promote osteoclastogenesis more efficiently than conventional CD28+ T-cells, which might contribute to the pathogenesis of systemic bone loss in RA and primary osteoporosis.


IL-15; T-lymphocyte; aging; osteoporosis; rheumatoid arthritis

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