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

Abstract

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. 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. 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. 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.