Circulating PD-1⁺CXCR5^-CD4⁺ 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-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.

SUBMITTER: Kamekura R 

PROVIDER: S-EPMC6649940 | biostudies-literature |

REPOSITORIES: biostudies-literature