Date: Monday, November 9, 2015
Session Title: T cell Biology and Targets in Autoimmune Disease Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
To study the influence of senescent CD28–T-cells on systemic osteoporosis in rheumatoid arthritis (RA) and patients with primary osteoporosis.
Prospective, cross-sectional study on 104 patients with RA (mean age 62.2 [±SD 12.6], 76% female, SDAI 13.5 [±10.2]) and 111 non-RA controls (mean age 60.7 [±11.3], 84.7% female). Bone mineral density (BMD) was determined by DEXA. PBMCs were retrieved at the same day of BMD measurement and were stained with anti-RANKL, CD3, CD4, CD8, CD45RA, CD45RO and/or CD28 mAbs to measure surface and intracellular expression of RANKL on T-cells and to determine the prevalence of T-cell subsets by flow cytometry. The capacity of T-cell subsets to induce osteoclastogenesis was assessed via TRAP staining in the presence of monocytes and M-CSF (25ng/ml) in vitro.
A reduced BMD as determined by DEXA was found in 58.1% of RA patients (14% with osteoporosis, 44.1% with osteopenia) and 56.1% of non-RA controls (38.8% with osteoporosis, 17.3% with osteopenia). RA patients with reduced BMD had higher prevalences of circulating CD4+CD28– (3.2% [0.1–41.2] vs. 0.7% [0.1–33.9], p=0.048). In non-RA controls we observed the same effect (3.5% [0.1–30.4] vs. 1.3% [0.1–34], p=0.032).
Surface RANKL expression was higher on CD4+CD28– T-cells (3.1% [0-57.9]) compared to naïve CD4+CD28+CD45RA+ (1.5 [0-45.3], p<0.001) and memory CD4+CD28+CD45RO+ (1.9 [0-38], p=0.006) T-cells. Moreover, surface RANKL expression was higher in RA patients than non-RA controls in all T-cell subsets (all p<0.05). After stimulation with anti-CD3 antibody, RANKL production was higher in CD4+CD28– T-cells (intracellular RANKL MFI: 870.2 [±205.9]) compared to naïve CD4+CD28+CD45RA+ (713 [±182.3], p=0.001) T-cells, whereas RANKL levels were similar in CD4+CD28– T-cells and memory CD4+CD28+CD45RO+ (862.2 [±289.7], p=0.207) T-cells. Similar results were obtained after stimulation with PHA or ConA.
The in vitro ability of T-cell subsets to induce osteoclastogenesis was higher in senescent CD28– T-cells compared to their CD28+ counterparts as indicated by TRAP-staining ((27.5 [±15.8] TRAP positive cells vs. 20.5 [±7.9], p=0.128).
Senescent CD28– T-cells are linked with the occurrence of systemic bone loss. Increased expression of RANKL on CD4+CD28– T-cells compared to other T-cell subsets may result in higher direct stimulation of osteoclastogenesis by this subset.
To cite this abstract in AMA style:Fessler J, Husic R, Lerchbaum E, Schwetz V, Stiegler C, Obermayer-Pietsch B, Graninger WB, Dejaco C. Senescent T-Cells Expedite RANKL-Dependent Bone Loss in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/senescent-t-cells-expedite-rankl-dependent-bone-loss-in-rheumatoid-arthritis/. Accessed May 8, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/senescent-t-cells-expedite-rankl-dependent-bone-loss-in-rheumatoid-arthritis/