Date: Sunday, November 8, 2020
Session Type: Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Inflammatory arthritis is characterized by chronic inflammation of joints which can be suppressed with immunomodulatory therapy. However, two-thirds of patients will have an arthritis flare when medication is stopped. We sought to understand how immune cells that persist in arthritic joints in remission may contribute to subsequent recurrence of disease.
Methods: Using IL-1 receptor antagonist (IL-1Ra)-deficient mice, a spontaneous model of T cell mediated arthritis, we identified animals early in arthritis who exhibit involvement of only one of paired major joints (ankle, wrist). We induced arthritis remission by administration of anakinra, an IL-1Ra analog, and then observed flare pattern when treatment was discontinued. Synovium was dissected from the mice and evaluated for the presence of T cell subsets by flow cytometry. Intraperitoneal injection of anti-Thy1.2 antibodies was utilized to deplete circulating T cells and assess tissue residency.
Results: In IL-1Ra deficient mice, unilateral joint inflammation is suppressed by treatment with anakinra. Intriguingly, subsequent discontinuation of therapy results in arthritis flare preferentially in the originally-inflamed joint, implying a mechanism of joint-specific memory. We identified a population of T cells with a cell surface protein signature consistent with resident memory T cells (CD44+CD62L-CD69+CD103+) is found in the synovium during remission. These cells are only present in joints that were previously inflamed, and persist in the synovium despite antibody-mediated depletion of circulating T lymphocytes, suggesting tissue residency.
Conclusion: Our data suggests that the persistence of T cells with a resident memory phenotype in the synovium of arthritic joints may contribute to arthritis flares when immunomodulatory medication is weaned.
To cite this abstract in AMA style:Levescot A, Chang M, Wactor A, Blaustein R, Nelson-Maney N, Fuhlbrigge R, Nigrovic P. Resident Memory T Cells Persist in Joints of Anakinra-Treated Mice in Spontaneous Arthritis Model [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/resident-memory-t-cells-persist-in-joints-of-anakinra-treated-mice-in-spontaneous-arthritis-model/. Accessed April 16, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/resident-memory-t-cells-persist-in-joints-of-anakinra-treated-mice-in-spontaneous-arthritis-model/