AUTHOR=Fessler Johannes , Husic Rusmir , Schwetz Verena , Lerchbaum Elisabeth , Aberer Felix , Fasching Patrizia , Ficjan Anja , Obermayer-Pietsch Barbara , Duftner Christina , Graninger Winfried , Stradner Martin Helmut , Dejaco Christian 

TITLE=Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00095

DOI=10.3389/fimmu.2018.00095

ISSN=1664-3224

ABSTRACT=Objective: T-cells are critical players in the pathogenesis of osteoporosis in patients with rheumatoid Arthritis (RA). Premature senescence of lymphocytes including 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.
Methods: 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 (DXA) scan. Flow cytometry, magnetic-associated cell sorting and cell culture experiments were performed to analyze the pro-osteoclastic phenotype and function of senescent CD4+CD28- T-cells.
Results: 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. RANKL was expressed at higher levels on CD4+CD28- T-cells as compared to CD28+ T-cells. Stimulation with IL-15 led to an upregulation of RANKL expression, particularly on CD28- T-cells. CD4+CD28- T-cells induced osteoclastogenesis more efficiently than CD28+ T-cells.
Conclusion: 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.