Circulating PD-1(+)CXCR5(−)CD4(+) T cells underlying the immunological mechanisms of IgG4-related disease

OBJECTIVE: The aim was to study the pathological role of lymphocytes with a peripheral T helper-cell-like 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.