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Transcript: Paper 2: Cytotoxic CD8+ t cells target citrullinated antigens in RA Compared in PB Paper Overview: 1. The Normal Synovium - (D. Smith, 2011) 2. Cytotoxic CD8+ T cells target citrullinated antigens in RA pateints - (Moon et al., 2023b) 3. Human memory T cells with a naive phenotype accumulate with aging and repsond to persistent virsues - (Pulko et al., 2016) Figure 1: Flow cytommetry and dot plot results from Aim: 1. Characterise CD8+ T cell 2. Idenitfy clonally expanded Cd8+ T cell lineages Findings: CD8+ Expanded in ACPA+ pateints Strong positive corrolation between CD8+ T cell popualtion and Anti-Citrullinated protien Ab level --> both immune arms responding to arm antigen Phenotypically " cytotoxic + destructive" Decreased naive cells and Elevated effector cells --> consistent with chronic infection Moon, J.-S., Younis, S., Ramadoss, N. S., Iyer, R., Sheth, K., Sharpe, O., Rao, N. L., Becart, S., Carman, J. A., James, E. A., Buckner, J. H., Deane, K. D., Holers, V. M., Goodman, S. M., Donlin, L. T., Davis, M. M., & Robinson, W. H. (2023a). Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Nature Communications, 14(1), 319. https://doi.org/10.1038/s41467-022-35264-8 Subset of Imposter T cells?? Paper reviews Typical Joint Structure Thank you!! Questions? Refrences: D. Smith, M. (2011). The Normal Synovium. The Open Rheumatology Journal, 5(1), 100–106. https://doi.org/10.2174/1874312901105010100 Heslington, A., Catharien M. U. Hilkens, Ferreira, A. M., & Melo, P. (2025). Functional Synovium‐Based 3D Models in the Context of Human Disease and Inflammation. Advanced NanoBiomed Research. https://doi.org/10.1002/anbr.202500029Moon, J. S., Younis, S., Ramadoss, N. S., Iyer, R., Sheth, K., Sharpe, O., Rao, N. L., Becart, S., Carman, J. A., James, E. A., Buckner, J. H., Deane, K. D., Holers, V. M., Goodman, S. M., Donlin, L. T., Davis, M. M., & Robinson, W. H. (2023). Cytotoxic CD8+ T cells target citrullinated antigens in rheumatoid arthritis. Nature Communications, 14(1), 319. https://doi.org/10.1038/s41467-022-35264-8Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., Billheimer, D., Haddad, E. K., Murray, K. O., Wertheimer, A. M., & Nikolich-Žugich, J. (2016). Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nature Immunology, 17(8), 966–975. https://doi.org/10.1038/ni.3483 Paper 3: Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses (Heslington et al., 2025) Paper 1: The Normal Synovium TMNP cells form a unique T cell subset with naive phenotype and higher expression of CD49d and CXCR3 than that of TN cells Healthy: Intimal MLS Diseased: intimal MLS Marcophages stained for CD68+ Pulko, V., Davies, J. S., Martinez, C., Lanteri, M. C., Busch, M. P., Diamond, M. S., Knox, K., Bush, E. C., Sims, P. A., Sinari, S., Billheimer, D., Haddad, E. K., Murray, K. O., Wertheimer, A. M., & Nikolich-Žugich, J. (2016). Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. Nature Immunology, 17(8), 966–975. https://doi.org/10.1038/ni.3483 Healthy : Intimal FLS Diseased: Intimal FLS Fibroblasts stained for CD55+ Smith, M. D. (2011). The normal synovium. Open Rheumatology Journal, 5(Suppl 1: M2), 100–106. https://doi.org/10.2174/1874312901105010100