Session Information
Date: Sunday, November 8, 2026
Title: (0009-0021) T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster A
Session Type: Poster Session A
Session Time: 10:30AM-12:30PM
Background/Purpose: Systemic lupus erythematosus (SLE) patients are found to generate a dysregulated immunological architecture and can be stratified according to immunophenotype or transcriptomic profiles. Our aim is to uncover the immunological features of SLE and explore cell subsets with therapeutic and prognostic potentials.
Methods: Newly-diagnosed SLE patients were enrolled with a median follow-up of 5 years. Machine learning was employed to discern immunological features of patients, stratify them accordingly, and identify the most prognostic cell subset. We performed single-cell RNA sequencing to further investigate PD-1⁺CD8⁺ T cells. Flow cytometry and functional assays were then applied to validate the transcriptomic findings and explore the effects of PD-1 agonist.
Results: SLE patients exhibited distinct immunological profiles compared to healthy donors and can be stratified into two clusters based on peripheral immune cell composition. This stratification correlated with distinct clinical characteristics and prognoses. Among subsets contributing to classification, an elevated frequency of PD-1⁺CD8⁺ T cells was most strongly associated with an unfavorable disease prognosis. Multivariate analysis confirmed the frequency of these cells as an independent prognostic factor in SLE. Compared to their PD-1⁻ counterparts, PD-1⁺CD8⁺ T cells displayed a hyperactivated phenotype, characterized by enhanced inflammatory and cytotoxic signatures, upregulation of interferon and complement pathways, and dysregulated metabolism, suggesting their role as pathological effector cells in SLE. Furthermore, in vitro treatment with a PD-1 agonist effectively reduced both the frequency and effector functions of PD-1⁺CD8⁺ T cells.
Conclusion: Our study identifies hyperactivated PD-1⁺CD8⁺ T cells as a prominent feature of immune dysregulation in SLE, which are strongly implicated in disease activity and poor prognosis. The finding regarding PD-1 agonist reveals a promising therapeutic avenue for SLE.
To cite this abstract in AMA style:
Wu C, Chen S, Ye S, Zhang X, Fu Q. PD-1+CD8+ T cells are hyperactivated and associated with refractory systemic lupus erythematosus [abstract]. Arthritis Rheumatol. 2026; 78 (suppl 9). https://acrabstracts.org/abstract/pd-1cd8-t-cells-are-hyperactivated-and-associated-with-refractory-systemic-lupus-erythematosus/. Accessed .ACR Meeting Abstracts - https://acrabstracts.org/abstract/pd-1cd8-t-cells-are-hyperactivated-and-associated-with-refractory-systemic-lupus-erythematosus/