Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

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.