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.
Colley
D G
DG
Center for Tropical and Emerging Global Diseases and the Department of Microbiology, University of Georgia, Athens, GA 30602, USA. dcolley@uga.edu
Sasser
L E
LE
Reed
A M
AM
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis*; D018122:B7-1 Antigen / Q000032:analysis*; D018845:CD11 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology*
D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018845:CD11 Antigens; D017252:CD3 Complex; C556977:PDCD1LG2 protein, human; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D017493:Leukocyte Common Antigens