Chronic schistosomiasis: Dendritic cells generated from patients can overcome antigen-specific T cell hyporesponsiveness

Abstract

Chronic infection with helminths is associated with down-regulated antigen-specific T cell responses. In order to determine whether schistosome- specific T cells are present, yet functionally unresponsive, or absent in the periphery of chronically infected persons, autologous granulocyte-macrophage colony-stimulating factor and dendritic cells (DC) derived from interleukin (IL)-4 were used as highly efficient antigen-presenting cells (APC). Peripheral blood mononuclear cells (PBMC) from persons harboring Schistosoma haematobium infection and hyporesponsive to parasite antigen were cocultured with autologous DC in the presence of adult worm antigen (AWA). In contrast to PBMC alone, DC-supplemented cultures responded to AWA by proliferation and by IL-4 and IL-5 production and, in some patients, by production of interferon-γ. Thus, schistosome-specific T helper cells are present in the periphery but are functionally hyporesponsive during active infection with schistosomes. Cytokine responses representing the Th1 and (more importantly) Th2 types can be restored in vitro when DC are used as APC.