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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 | 2018

REPOSITORIES: biostudies-literature

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Publications

Circulating PD-1<sup>+</sup>CXCR5<sup>-</sup>CD4<sup>+</sup> T cells underlying the immunological mechanisms of IgG4-related disease.

Kamekura Ryuta R   Yamamoto Motohisa M   Takano Kenichi K   Yabe Hayato H   Ito Fumie F   Ikegami Ippei I   Takaki Hiromi H   Shigehara Katsunori K   Suzuki Chisako C   Himi Tetsuo T   Takahashi Hiroki H   Ichimiya Shingo S  

Rheumatology advances in practice 20181017 2


<h4>Objective</h4>The aim was to study the pathological role of lymphocytes with a peripheral T helper-cell-like phenotype (PD-1<sup>+</sup>CXCR5<sup>-</sup>CD4<sup>+</sup>) in IgG4-related disease (IgG4-RD).<h4>Methods</h4>PD-1<sup>+</sup>CXCR5<sup>-</sup>CD4<sup>+</sup> T cells in the blood of patients with IgG4-RD (<i>n</i> = 53), patients with SS (<i>n</i> = 16) and healthy volunteers (<i>n</i> = 34) as controls were analysed by flow cytometry. Correlations between results obtained by flow c  ...[more]

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