Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: PD-1 is a co-inhibitory transmembrane protein with a significant effect on immune regulation. Several studies have shown elevated expression levels of PD-1 on T cells isolated from the blood and the synovial fluid of patients with rheumatoid arthritis (RA). Moreover, in some studies, PD-1 expression levels correlated with disease activity scores. The goal of our study was to uncover the signaling pathways downstream of PD-1 in RA T cells as well as its contribution to cellular function. Understanding the biology of PD-1 in RA T cells may lead to novel targets in the treatment of inflammatory arthritis.
Methods: Naïve primary T cells were isolated from RA patients and healthy controls. PD-1 expression was measured by flow cytometry. T cells were stimulated with beads coated with antibodies to T cell receptors as well as PD-L2, a ligand for PD-1. Western blot analysis was used to measure levels of key signaling proteins. Cytokine secretion, calcium influx, and adhesion to coated surfaces were concurrently recorded. Correlation analysis between these variables and clinical parameters were performed.
Results: Compared with healthy controls, T cells isolated from RA patients demonstrate higher plasma membrane PD-1 levels, which correlate with disease activity. When stimulated, these cells secrete more IL-2 in response to T cell receptor ligation, while concurrent PD-1 receptor activation led to an attenuated response. Higher levels of phosphorylated Erk were recorded in RA T cells compared to healthy control T cells. Moreover, stimulation of PD-1 led to Erk inhibition only in the RA T cells, but not in the cells isolated from healthy controls.
Conclusion: Given that PD-1 is a co-inhibitory receptor, one might expect that T cells from patients with autoimmune disease would express lower levels of PD-1 on their surface. In contrast, our data suggests that RA T cells express higher levels of PD-1 and that they are more activated when compared to healthy control T cells. It is not clear whether PD-1 is a cell surface marker of activation or if those T cells are “resistant” to signals downstream of PD-1. In conclusion, PD-1 may serve as a T cell regulator in RA with possible therapeutic potential.
To cite this abstract in AMA style:Sandigursky S, Mor A. Programmed Cell Death (PD)-1 May Play a Significant Role in the Pathogenesis of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/programmed-cell-death-pd-1-may-play-a-significant-role-in-the-pathogenesis-of-rheumatoid-arthritis/. Accessed July 2, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/programmed-cell-death-pd-1-may-play-a-significant-role-in-the-pathogenesis-of-rheumatoid-arthritis/