Proinflammatory Features of Stem Cell-like Memory T Cells from Human Patients with Rheumatoid Arthritis

Stem cell-like memory T (Tscm) cells are a subset of memory T cells that have characteristics of stem cells. The characteristics of Tscm cells in patients with rheumatoid arthritis (RA) are not well known. The percentage of CD4⁺ and CD8⁺ Tscm cells in PBMCs and synovial fluid mononuclear cells was measured. After confirming the stem cell nature of Tscm cells, we examined their pathogenicity in RA patients and healthy controls (HCs) by assessing T cell activation markers and cytokine secretion after stimulation with anti-CD3/CD28 beads and/or IL-6. Finally, RNA transcriptome patterns in Tscm cells from RA patients were compared with those in HCs. In this study, the percentage of CD4⁺ and CD8⁺ Tscm cells in total T cells was significantly higher in RA patients than in HCs. Tscm cells self-proliferated and differentiated into memory and effector T cell subsets when stimulated. Compared with Tscm cells from HCs, Tscm cells from RA patients were more easily activated by anti-CD3/CD28 beads augmented by IL-6. Transcriptome analyses revealed that Tscm cells from RA patients showed a pattern distinct from those in HCs; RA-specific transcriptome patterns were not completely resolved in RA patients in complete clinical remission. In conclusion, Tscm cells from RA patients show a transcriptionally distinct pattern and are easily activated to produce inflammatory cytokines when stimulated by TCRs in the presence of IL-6. Tscm cells can be a continuous source of pathogenicity in RA.