Infusion of Dendritic Cells Carrying Donor Lymphocytes Treated With 8-Methoxypsoralen and Ultraviolet A Light Induces CD19+IL-10+ Regulatory B cells and Promotes Skin Allograft Survival

PUVA-SP DCs are immature dendritic cells (imDCs) that have taken up donor splenic lymphocytes treated with 8-methoxypsoralen and ultraviolet A light (PUVA-SPs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient imDCs, and infusion of PUVA-SP DCs can induce CD4+CD25highFoxp3+ regulatory T cells (Treg). However, the regulatory effect of PUVA-SP DCs on B cells is poorly understood. In this study, we compared PUVA-SP DCs with imDCs in terms of lipopolysaccharide (LPS) responsiveness and flow cytometric analysis of interleukin (IL) 10 expression in splenic CD19+B cells. Our results demonstrate that PUVA-SP DCs can suppress subsequent LPS-induced DC maturation and that infusion of PUVA-SP DCs, in the absence of an immunosuppressant, significantly promotes skin allograft survival. This effect was associated with up-regulation of circulating regulatory B cells exhibiting preferential IL-10 secretion. Our results suggest that effective treatments involving infusion of PUVA-SP DCs is likely related to the modulation not only of T-cell and Treg functions but also of B-cell and regulatory B-cell (Breg) functions.