Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis

Abstract

During visceral leishmaniasis (VL), Th1-based inflammation is induced to control intracellular parasites. Inflammation-based pathology was shown to be dampened by IL-10 and eventual programmed death 1–mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell–produced IL-10 during VL are unknown. CD19+, CD5−, CD1d−, IgDhi regulatory B cells from healthy controls produced IL-10 in the absence of infection or stimulation, in contrast to IgDlo/neg B cells. IgDhi B cells may have a de novo versus induced regulatory program. The population of IgDhi B cells increased 3-fold as VL progressed. B cells from VL dogs were necessary and sufficient to suppress Th1 cell effector function. IgDhi B cells induced IL-10 production by T cells and IgDlo B cells. Blockage of B cell–specific PD-L1 restored Th1 responses. IgDhi regulatory B cells represent a novel regulatory B cell that may precipitate T cell exhaustion during VL.