T follicular helper 1 cells in blood potentially mirror salivary gland-infiltrating T cells in Sjögren’s disease

This study aimed to characterize CD4+ T cell subsets in peripheral blood that mirror the inflammatory milieu of labial salivary glands (LSG) in primary Sjögren’s disease (pSjD). Using multicolor flow cytometry and T cell receptor (TCR) sequencing, we identified CXCR3+CXCR5+ T follicular helper 1 (Tfh1) cells as significantly elevated in the circulation of pSjD patients and even more prominently increased in the LSG, with blood PD-1+ICOS+ Tfh1 cells positively correlating with titers of antinuclear, anti-SS-A, and anti-SS-B antibodies.

In contrast, CXCR3+CXCR5− Th1 cells were enriched in LSG but reduced in circulation. TCR analysis demonstrated that circulating Tfh1 cells shared extensive clonal similarity with LSG T cells. In the LSG, cytokines such as IL-6, IL-12, IL-21, and TGF-β were upregulated, with TGF-β and TCR recognition promoting Tfh1 differentiation.