Background/Purpose: Following infection, resident memory CD8+ T cells (T_RM) 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 T_RM 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 T_RM 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 T_RM 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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/joint-cd8-tissue-resident-memory-cell-activation-produces-local-inflammatory-arthritis/