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Research article
Eun Bong Lee
Seoul National University College of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0703-1208
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Stem cell-like memory T cells (Tscm) are a subset of memory T cells that have the characteristics of stem cells. The role of Tscm cells in rheumatoid arthritis (RA) is not well characterized.
Methods: After measuring percentages of CD4+ and CD8+ Tscm cells within the peripheral blood and synovial mononuclear cell populations in RA and health controls (HCs), we confirmed the stem cell nature of Tscm cells from RA patients. The association of Tscm cells with disease activity was also analyzed. Next, the pathogenicity of Tscm cells was examined in RA patients by assessing T cell activation markers and cytokine secretion after stimulation with IL-6 and anti-CD3/CD28 beads. Finally, the transcriptomes of Tscm cells from RA patients were compared with those from HCs.
Results: The percentages of CD4+ and CD8+ Tscm cells among total T cells were significantly higher in RA patients than in HCs. Upon stimulation, Tscm cells from RA patients differentiated into daughter T cell subsets with self-renewal capacity. The percentage of CD4+ Tscm cells correlated with expression of RA disease activity markers. Tscm cells from RA patients were more easily activated by IL-6 and anti-CD3/CD28 beads than those from HCs. Transcriptome analysis revealed that Tscm cells from RA patients showed patterns distinct from those of HCs.
Conclusion: The percentage of transcriptionally distinct and potentially pathogenic Tscm cells are higher in RA patients than in HCs; these cells may be a continuous source of pathogenic T cells, which perpetuate RA.
Keywords
Stem cell-like memory T cells, Rheumatoid arthritis, IL-6, Remission
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This is a preprint. It has not completed peer review.
Research article
Eun Bong Lee
Seoul National University College of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0703-1208
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 11 Feb, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Rheumatology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Stem cell-like memory T cells (Tscm) are a subset of memory T cells that have the characteristics of stem cells. The role of Tscm cells in rheumatoid arthritis (RA) is not well characterized.
Methods: After measuring percentages of CD4+ and CD8+ Tscm cells within the peripheral blood and synovial mononuclear cell populations in RA and health controls (HCs), we confirmed the stem cell nature of Tscm cells from RA patients. The association of Tscm cells with disease activity was also analyzed. Next, the pathogenicity of Tscm cells was examined in RA patients by assessing T cell activation markers and cytokine secretion after stimulation with IL-6 and anti-CD3/CD28 beads. Finally, the transcriptomes of Tscm cells from RA patients were compared with those from HCs.
Results: The percentages of CD4+ and CD8+ Tscm cells among total T cells were significantly higher in RA patients than in HCs. Upon stimulation, Tscm cells from RA patients differentiated into daughter T cell subsets with self-renewal capacity. The percentage of CD4+ Tscm cells correlated with expression of RA disease activity markers. Tscm cells from RA patients were more easily activated by IL-6 and anti-CD3/CD28 beads than those from HCs. Transcriptome analysis revealed that Tscm cells from RA patients showed patterns distinct from those of HCs.
Conclusion: The percentage of transcriptionally distinct and potentially pathogenic Tscm cells are higher in RA patients than in HCs; these cells may be a continuous source of pathogenic T cells, which perpetuate RA.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
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