APC from mice harbouring the filarial nematode, Brugia malayi, prevent cellular proliferation but not cytokine production

Abstract

Specific T cell hyporesponsiveness and depressed antibody production is a key feature of human infection with the filarial nematodes, Brugia malayi and Wuchereria bancrofti. Despite this immune suppression, responses indicative of Th2 subset activation are present, including unusually high levels of specific IgG4. We tested the possibility that infection with filarial nematodes causes a reduction in the co-stimulatory or antigen-presenting capacity of macrophages resulting in a failure to activate specific T cells. Adherent peritoneal exudate cells (PEC) from mice implanted with adult B. Malayi were used to present antigen to the conalbumin-specific T cell clone, D10.G4. Proliferation of the D10 cells at even background levels was completely blocked by the presence of implant-derived adherent PEC. However, cytokine production by these cells in response to antigen was intact, and thus PEC from implanted mice are capable of functionally processing and presenting antigen. The elicitation of a suppressive cell population was specific for live adults as cells from mice implanted with dead adult parasites effectively stimulated D10 proliferation. The block in cellular proliferation is not due to the production of factors typically associated with macrophage suppression such as nitric oxide, prostaglandins or catalase. These observations are consistent with the T cell hyporesponsiveness seen in human cases of patent Brugia infection and may provide a murine model for the immune suppression seen in lymphatic filariasis.