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Expression of PD\u20101 and PD\u2010L2 on T cells, B cells, and macrophages was quantified by flow cytometry. The effects of blockade of PD\u20101 and PD\u2010L2 were analyzed by microfluidic ELISA (micro\u2010ELISA), a technique that can measure very low amounts of cytokines. In addition, the effects of sPD\u20101 and sPD\u2010L2 on disease progression were assessed in mice with topo I\u2013induced SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum levels of sPD\u20101 and sPD\u2010L2 were elevated in patients with SSc and correlated with the extent of fibrosis and immunologic abnormalities. Expression levels of PD\u20101 and PD\u2010L2 were significantly elevated on SSc T cells, B cells, and macrophages. Micro\u2010ELISA analysis of serum samples from patients with SSc showed that PD\u2010L2<jats:sup>high<\/jats:sup> B cells had higher levels of interleukin\u201010 (IL\u201010) production compared with PD\u2010L2<jats:sup>low<\/jats:sup> B cells, indicating that PD\u2010L2 acts as a regulator of T cell cytokine production via cognate interactions with T cells and B cells. In mice with topo I\u2013induced SSc, production of IL\u201010 by topo I\u2013specific B cells in cultures with T cells and topo I protein was significantly higher than that by conventional B cells, and intraperitoneal injection of recombinant chimeric PD\u20101\u2010Fc and PD\u2010L2\u2010Fc canceled these enhanced effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that sPD\u20101 and sPD\u2010L2 contribute to disease development in SSc via the regulation of cognate interactions with T cells and B cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40164","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T11:12:45Z","timestamp":1495797165000},"page":"1879-1890","source":"Crossref","is-referenced-by-count":68,"title":["Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic 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