Altered levels of circulating CD8+CXCR5+PD-1+T follicular cytotoxic cells in primary Sjögren's syndrome

Abstract

Background: Circulating CD8⁺ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) (CD8⁺CXCR5⁺T), a recently identified follicular cytotoxic T cell subset, are involved in antiviral immunity and autoimmunity, but their abundance and role in the pathogenesis of primary Sjögren syndrome (pSS) are unknown.

Methods: Circulating CD8⁺CXCR5⁺T cell and CD8⁺ regulatory T cells (CD8⁺Treg) were evaluated in 49 pSS patients (19 patients with pulmonary involvement) and 24 age- and sex-matched healthy controls (HCs) by flow cytometry. Orthogonal partial least squares discriminant analysis (OPLS-DA) was performed, and receiver operating characteristic curves (ROC) were generated to identify characteristic cell subsets. Spearman's correlation analysis was conducted to examine the relationships between CD8⁺ T cell subsets and clinical features.

Results: The proportions and numbers of CD8⁺CXCR5⁺, CD8 + CXCR5⁺ programmed death 1-positive (PD-1⁺), and CD8⁺CXCR5^-PD-1⁺T cells were significantly higher, whereas those of CD8⁺Treg were markedly lower, in pSS patients than HCs. The CD8⁺CXCR5⁺PD-1⁺T cell to CD8⁺Treg ratio had the greatest discriminatory power for pSS and HCs according to OPLS-DA and ROC analyses. The increased numbers of CD8⁺CXCR5⁺T cells and CD8⁺CXCR5⁺PD-1⁺T cells were strongly associated with those of CD4⁺CXCR5⁺T and B cells. The proportions and numbers of CD8⁺CXCR5⁺PD-1⁺T cells were increased in pSS patients with lung involvement.

Conclusions: We identified a new CD8⁺CXCR5⁺PD-1⁺T subset, which was increased in abundance in pSS patients, particularly those with lung involvement, compared with HCs. Also, the CD8⁺CXCR5⁺PD-1⁺T to CD8⁺Treg ratio may be useful for identifying pSS. Our findings suggest that targeting follicular CD8⁺T cell subsets has therapeutic potential for pSS. Key Points • CD8+CXCR5+ T cells were expanded in the circulation of patients with pSS. • Reduced numbers CD8+Treg cells in pSS patients. • Increased CD8+CXCR5+PD-1+T cells in pSS patients with pulmonary involvement.

Keywords: CD8+ regulatory T cells; CD8+CXCR5+ follicular cytotoxic T subsets; Lung involvement; OPLS-DA; Primary Sjögren’s syndrome.