OP0072 SINGLE CELL SEQUENCING REVEALS CLONALLY EXPANDED CYTOTOXIC CD4+ T CELLS IN THE JOINTS OF ACPA+ RA PATIENTS

Background: CD4+ T cells with cytotoxic functions (CD4+ CTL) have gained attention in recent years. Accumulating evidence supports their importance defense against human viral infections such as CMV 1 , EBV 2 dengue 3 HIV 4, 5 and SARS-CoV-2 6 . Moreover, expansion of so called CD28null been reported the blood patients rheumatic diseases rheumatoid arthritis (RA) 7 myositis 8 vasculitis 9 well cardiovascular 10 Objectives: Here, we aimed to investigate presence clonal CTL peripheral (PB) synovial fluid (SF) RA using single cell technologies. Methods: We assessed expression effector molecules transcription factors (n=21) paired (n=16) from ACPA- APCA+ by multi-parameter flow cytometry. performed sequencing, combination 5´ TCRab on purified ACPA+ (n=7). Results: Flow cytometry experiments show that Granzyme-B+ Perforin-1+ are significantly increased SF compared (p=0.0072). The could be confirmed sequencing each patient tested found adhesion G-protein coupled receptor GPR56 is selectively expressed recently described helper (T PH ) T-cell subset 11 associates tissue resident memory markers LAG-3, CXCR6 CD69. In blood, a previous report 12 showing delineates cells. Finally, expanded TCR clones expressing were identified and, for some patients, corresponding blood. Conclusion: marker residency receptors. highlights suggests potential therapeutic target (Figure 1). References: [1]Casazza J. P. et al ., J Exp Med 2006, 203 (13), 2865-77. [2]Landais E. al., Blood 2004, 103 (4), 1408-16. [3]Kurane I. 1989, 170 (3), 763-75. [4]Appay V. Immunol 2002, 168 (11), 5954-8. [5]Juno A. Front 2017, 19. [6]Meckiff B. Cell 2020, 183 (5), 1340-1353 e16. [7]Schmidt D. Clin Invest 1996, 97 (9), 2027-37. [8]Fasth 2009, (7), 4792-9. [9]Moosig F. 1998, 114 (1), 113-8. [10]Sato K. 239-50. [11]Rao A., Nature 542 (7639), 110-114. [12]Peng Y. M. Leukoc Biol 2011, 90 735-40. Acknowledgements: thank who donated samples medical staff at Rheumatology Clinic Karolinska University Hospital. Julia Boström, Gloria Rostvall, Susana Hernandez Machado acknowledged organizing sampling, storage, administration biomaterial. This study supported grants Dr. Margaretha Nilssons, Nanna Svartz, Ulla Gustaf af Ugglas foundations Swedish association rheumatism. Disclosure Interests: Alexandra Argyriou: None declared, Marc H Wadsworth II Employee of: Pfizer, Inc, Cambridge, MA 02139, United States, Adrian Lendvai: Stephen Christensen Aase Hensvold: Christina Gerstner: Kellie Kravarik Aaron Winkler Vivianne Malmström: Karine Chemin: declared