A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells

Although exogeneous "danger" signals such as LPS can activate APC to produc e a Th1 response, the nature of events initiating a Th2 response is controv ersial. We now show that pathogen-derived products have the capacity to ind uce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4(+) T cells toward either a Th1 o r Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 resp onse (increased generation of IFN-gamma and reduced production of IL-4) by Ag stimulated CD4(+) T cells from the D0.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323-339). In contrast, a phosphorylch oline-containing glycoprotein, ES-62, secreted by the filarial nematode, Ac anthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to ind uce Th2 responses (increased IL-4 and decreased IFN-gamma). In addition, we show that the switch to either Th1 or Th2 responses is not effected by dif ferential regulation through CD80 or CD86 and that a Th2 response is achiev ed in the presence of IL-12.