Enhanced co-expression of TIGIT and PD-1 on γδ T cells correlates with clinical features and laboratory parameters in patients with primary Sjögren's syndrome.

Objectives: The research aimed to assess the proportions of Gamma delta (γδ) T cells and the expression levels of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, Tim-3, and PD-1 on γδ T cells in the peripheral blood of patients diagnosed with primary Sjögren's syndrome (pSS), and to evaluate the clinical significance of these findings.

Methods: Utilizing flow cytometry, we investigated the proportion of γδ T cells and the expression of CD226, ICOS, CD40L, OX40, TIGIT, LAG-3, PD-1, and Tim-3 on γδ T cells in 37 patients diagnosed with pSS and 28 healthy controls (HC). Moreover, we explored the potential associations between the proportion of γδ T cells, TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells with clinical symptoms and laboratory parameters.

Results: Compared to HC, patients with pSS showed a decreased proportion of γδ T cells, alongside an increased proportion of TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells (p < 0.01). Nevertheless, there were no statistically significant variations noted in the expression levels of CD226, ICOS, CD40L, Tim-3, LAG-3, and OX40 on γδ T cells between two groups (p > 0.05). Furthermore, γδ T cells demonstrated a declining trend in patients with clinical symptoms such as xerostomia, xerophthalmia, decayed teeth, and fatigue, as well as in those with high IgG levels and positivity for anti-SSB/La, anti-SSA/Ro60, and anti-SSA/Ro52. Conversely, TIGIT + γδ T cells, PD-1 + γδ T cells, and TIGIT + PD-1 + γδ T cells exhibited an increasing trend in these patient groups. In correlation analyses with IgG, ESR, CRP, C3, C4, IgA, RF, IgM, and ESSDAI, γδ T cells were observed to have a negative correlation with ESR, IgG and ESSDAI. TIGIT + γδ T cells demonstrated significant positive correlations with IgG, IgA, and ESSDAI. PD-1 + γδ T cells showed positive correlations with ESR, CRP, IgA, and ESSDAI. Furthermore, TIGIT + PD-1 + γδ T cells showed significant positive correlations with ESR, IgG, RF, IgA, and ESSDAI.

Conclusion: Our results indicated that patients with pSS exhibited a reduction in γδ T cells alongside elevated expression of TIGIT, PD-1, and their co-expression on γδ T cells. These changes were found to correlate with clinical symptoms and laboratory parameters, suggesting that γδ T cells, TIGIT + γδ T cells, PD-1 + γδ T cells, and especially TIGIT + PD-1 + γδ T cells could potentially serve as diagnostic biomarkers for pSS.