Session Type: Poster Session D
Session Time: 8:30AM-10:30AM
Background/Purpose: Following infection, resident memory CD8+ T cells (TRM) populate tissues as long lived sentinel cells. Their aberrant activation can trigger relapsing inflammation in autoimmune diseases with a strong site- and tissue-specific component such as inflammatory arthritis. Virus specific CD8+ T cells are a recognized component of synovial fluid and synovial biopsies from individuals with autoimmune arthritis. Here, we demonstrate vesicular stomatitis virus encoding ovalbumin (VSV-OVA) specific CD8+ T cells in the mouse knee following resolution of acute infection. With antigen exposure, joint TRM proliferate and recruit additional immune cells preferentially to the site of activation.
Methods: OT1 lymphocytes express a transgenic TCR which recognizes the SIINFEKL peptide of ovalbumin. CD45.1+OT-1 cells are transferred intravascular (i.v.) to CD45.2+ C57BL/6 recipient mice. The next day, recipient mice received 106 PFU VSV-OVA i.v. Thirty days after infection, mice receive intra-articular (i.a.) SIINFEKL, PBS alone, or no injection. Knees are fixed, decalcified with EDTA, and frozen. Slides were stained with DAPI, anti-CD45.1, anti-collagen II, streptavidin-PE or streptavidin-C594, anti-B220, anti-Ly6G, and anti-CD4.
Results: Stimulation with SIINFEKL peptide induces proliferation of TRM in target joint but not in opposite joint as demonstrated by both increased OT-1 numbers and their proportion to all cells as identified by DAPI staining (Figure 1A). Increased OT-1 numbers are accompanied by increased B cells, Neutrophils, and CD4 cells within the joint space. (Figure 1B-D).
Conclusion: Following acute infection with VSV-OVA, CD45.1+ donor OT-1 cells populate both joint synovium at a timepoint well past resolution of acute infection. As with TRM at other sites, they proliferate in response to antigenic stimulation and recruit additional inflammatory cells to the joint space.
Slide1.jpeg”Figure 1. Intra-articular OT_1, B220, Ly6G, and CD4 enumeration. Connecting lines indicate paired knees from same indiivudal mouse. *,p < 0.01, ANOVA followed by Tukey’s multiple comparison.
To cite this abstract in AMA style:Lotfi-Emran S, Masopust D. Joint CD8+ Tissue Resident Memory Cell Activation Produces Local Inflammatory Arthritis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/joint-cd8-tissue-resident-memory-cell-activation-produces-local-inflammatory-arthritis/. Accessed November 26, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/joint-cd8-tissue-resident-memory-cell-activation-produces-local-inflammatory-arthritis/