Circulating PD-11CXCR52CD41 T cells underlying the immunological mechanisms of IgG4-related disease

Abstract

Objective. The aim was to study the pathological role of lymphocytes with a peripheral T helper-celllike phenotype (PD-1+CXCR5-CD4+) in IgG4-related disease (IgG4-RD). Methods. PD-1+CXCR5-CD4+ T cells in the blood of patients with IgG4-RD (n=53), patients with SS (n=16) and healthy volunteers (n=34) as controls were analysed by flow cytometry. Correlations between results obtained by flow cytometry and clinical parameters relevant to IgG4-RD were also analysed. Results. The percentage and absolute number of PD-1+CXCR5_ cells within total CD4+ T cells in IgG4-RD patients were significantly increased compared with those in healthy volunteers. Further analysis showed that there were marked positive correlations of the percentage of PD-1+CXCR5-CD4+ T cells with the serum level of IgG4 and the number of organs involved. Interestingly, granzyme A (GZMA)+ cells were enriched in PD-1+CXCR5-CD4+ T cells, and the percentage and absolute number of GZMA+PD- 1+CXCR5-CD4+ T cells were significantly elevated in IgG4-RD patients. Although no obvious change was observed in the percentage of total CD4+ T cells, the percentage and absolute number of PD- 1+CXCR5-CD4+ T cells decreased in accordance with a reduction of serum IgG4 level after treatment with glucocorticoids. Conclusion. In IgG4-RD, circulating CD4+ T-cell populations were composed of PD-1+CXCR5- cells, and the ratios of these cells were correlated with clinical manifestations of IgG4-RD. Further analysis of GZMA+PD-1+CXCR5-CD4+ T cells might lead to a deeper understanding of the pathogenesis of ectopic lymphoid follicles and the persistent inflammation in IgG4-RD.