Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: The vasculitic lesions in GCA are filled with differentiated effector T cells that sustain granuloma formation, vessel wall restructuring, neoangiogenesis and intimal hyperplasia. Persistent T cell effector functions are counterregulated by inhibitory immune receptors, such as programmed cell death-1 (PD-1), and PD-1+ T cells have been identified as the mediators of immune exhaustion in chronic viral infection and anti-tumor immunity and are the target of novel immunotherapy to unleash tumor-destroying immune responses. Conversely, failure to upregulate PD-1 may perpetuate chronic immune reactivity and could contribute to the relentless inflammation in GCA
Methods: Patients with biopsy-positive GCA and age and sex-matched controls were enrolled. GCA-affected temporal artery tissues were examined for the expression of PD-1 on T cells. Dynamics of PD-1 expression following T cell activation were examined ex vivo in CD4 T cells from GCA patients and healthy controls. PD-1+ and PD-1– CD4 T cells were sorted and examined for T cell effector functions (expression of the lineage-determining transcription factors RORγt, T-bet, GATA-3 and FoxP3, and intracellular cytokine stores).
Results: Frequencies of circulating PD-1+ CD4 T cells were significantly reduced in GCA patients (p<0.01). No PD-1–expressing cells were identified in normal, noninflamed human arteries, but in GCA affected temporal arteries almost all tissue-infiltrating T cells were positive for PD-1. In inflamed arteries, PD-1 expression on tissue-residing T cells was predictive for the thickness of the intimal layer (p<0.05) and correlated with the tissue expression of the proinflammatory cytokines IFN-γ (p<0.05) and IL-17 (p<0.01). Ex vivo, sustained PD-1 expression could be induced in CD4 T cells from GCA patients (p<0.05). PD-1+ and PD-1– CD4 T cells populations from healthy controls and GCA patients were sorted and compared for the expression of lineage-determining transcription factors, and the effector cytokines IFN-γ, IL-17 and IL-4. PD-1+ CD4+ T cells from GCA patients expressed higher levels of Th1 (p<0.05) and Th17 related genes (p<0.01).
Conclusion: In patients with GCA, T cells expressing the inhibitory immune receptor PD-1 are highly enriched in the vascular lesions. However, such PD-1+ T cells are not exhausted and, to the opposite, display strong immune-stimulatory functions, including remodeling of the vascular wall. In GCA the immunoprotective effects from PD-1–mediated downregulation of chronic immunity are lost, depriving the patient of the beneficial effects of the PD-1–dependent immune checkpoint.
To cite this abstract in AMA style:Watanabe R, Zhang H, Hosgur E, Berry G, Goronzy J, Weyand CM. PD-1–Expressing T Cells in GCA Fail to Promote Immune Tolerance Functions [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pd-1-expressing-t-cells-in-gca-fail-to-promote-immune-tolerance-functions/. Accessed October 19, 2021.
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