PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity.

Dendritic cells (DC) are critical antigen-presenting cells for the induction and control of immune responses. PD-L2 (B7-DC) is a regulatory ligand on subpopulations of DC, and binds to the co-regulatory receptor PD-1, present on some activated T lymphocytes, leading to down-regulation. We now show that very early during experimental schistosomiasis (by 5 weeks) a significantly higher proportion of splenic CD11c+/B220- DC express PD-L2, and by 6 weeks after infection a higher proportion of splenic CD4 T cells express PD-1. In this CBA/J mouse/Schistosoma mansoni chronic infection model we have shown that most mice develop moderate morbidity (Moderate Splenomegaly Syndrome, MSS), while some parallel-infected mice express different immune characteristics and die or develop severe morbidity (Hypersplenomegaly Syndrome, HSS). We now report a positive correlation between the proportion of splenic CD11c+/B220- DC that express PD-L2 and showing MSS. In contrast, there is an inverse correlation between the proportion of splenic CD3+/CD4+ T lymphocytes that express PD-1 and showing MSS. The data demonstrate that schistosomes can induce sustained elevated percentages of PD-L2-expressing, B220-negative DC. Furthermore, when this potentially immunoregulatory environment occurs chronically, infected mice are most likely to have developed MSS, expressing moderate morbidity.