CD15+ Myeloid Cells from Patients with Disseminated Coccidioidomycosis Inhibit CD4+ T Cell Proliferation 2260247

Introduction Valley fever (VF) is a respiratory disease caused by Coccidioides and is estimated to cost over 3 billion in medical costs annually. In VF, the infiltration of Ly6G+ cells into the lungs has been reported in mice and humans, but the role of these cells has not been fully uncovered. Ly6G+ cells share a phenotype with myeloid-derived suppressor cells (MDSCs), which suppress protective immunity. We previously showed, Ly6G+ cells enriched from the lungs of non-protected mice suppressed CD4+ T cell proliferation and exacerbated disease in vaccinated mice. Thus, a portion of the infiltrated Ly6G+ cells comprises MDSCs, which contribute to the pathogenesis. Parallelly, we have analyzed PBMCs from VF patients, to investigate whether these myeloid cells are immunosuppressive. We hypothesize CD15+ cells isolated from the PBMCs of disseminated patients suppress CD4+ T cell function to a greater extent than those isolated from recovered patients. Methods PBMCs from recovered (n = 18), pulmonary (n = 5), and disseminated (n = 11) VF patients were evaluated for CD15 + (HLA-DR-CD11b+CD15+). A functional assay was performed in recovered (n = 10), pulmonary (n = 4), and disseminated (n = 6) patients. CD15+ cells were enriched and combined with autologous CD4+ T cells at a 1:1 ratio with anti-CD3/CD28 beads for 72 hours. Results Flow cytometric analysis revealed that the composition of CD15+ myeloid cells in PBMCs from three patient cohorts was comparable, consistent with other reports of microbial infection. Indeed the CD15+ cells from disseminated patients suppressed a significantly higher percentage of CD4+ T cell proliferation than those from recovered and pulmonary patients. Conclusion These data demonstrate that CD15+ myeloid cells from disseminated patients suppress CD4+ T cells, a function shared with MDSCs. This discovery is parallel to our previous report that MDSCs are recruited into the lungs and exacerbate disease in Coccidioides-infected mice. Our data provide an insight on the role of CD15+ myeloid cells in VF.