Session Type: Abstract Submissions
Session Time: 2:00PM-3:00PM
Methods: Methylated bovine serum albumin (meBSA) or ovalbumin (OVA) is injected into the wrist, knee and ankle joints of B6 mice. The contralateral side was injected with vehicle as a negative control. For the OVA conditions, 5×10^6 CD3+ cells collected from peripheral lymph nodes of OT-I mice were transferred IV into the mice 1 day prior to intra-articular OVA injection. Interleukin-1 was concurrently injected into the footpad of the mice to stimulate the immune response. Arthritis flare was triggered by i.p. meBSA or OVA re-stimulation. At days 7 (acute inflammation), 28 (remission) and 31 (flare), the joints were analyzed for inflammation by measuring joint thickness, histological evaluation, and flow cytometry analysis of disaggregated synovium.
Results: 7 days after injection, there is measureable swelling and histological evidence of synovitis, specifically in the joints exposed to the antigen. In the synovium, there is a corresponding increase in CD4 and CD8 T cell populations. At 28 days after injection, inflammation subsides with normalization of both joint size and resolution of synovitis. During this post-inflammatory remission, we found a persistent population of antigen-specific cells with resident memory T cell (TRM) phenotype (CD45.2+CD3+CD8+CD44+CD62L-CD69+CD103+). These TRM cells are preferentially increased in the synovium of the joint exposed to antigen. Upon intraperitoneal challenge with antigen, there is a recurrent inflammation specifically in the joints previously exposed to antigen, and a corresponding expansion of antigen-specific CD8+ TRM cells in the synovium is also seen.
Conclusion: Here, we created an inducible model of recurrent, joint-specific inflammation. Our data suggests synovial resident memory T cells may represent the basis for joint-specific memory in inflammatory arthritis.
To cite this abstract in AMA style:Chang MH, Levescot A, Morris A, Nelson-Maney N, Fuhlbrigge R, Nigrovic PA. Murine Model of Arthritis Flare Identifies CD8+ Tissue Resident Memory T Cells in Recurrent Synovitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). http://acrabstracts.org/abstract/murine-model-of-arthritis-flare-identifies-cd8-tissue-resident-memory-t-cells-in-recurrent-synovitis/. Accessed March 24, 2018.
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