Profound suppression of cellular proliferation mediated by the secretions of nematodes

Abstract

Loss of T lymphocyte proliferation and the emergence of a host response that is dominated by a Th2-type profile are well-established features of human filarial infection. Down-regulation and modulation of host T cell responses during lymphatic filariasis has been investigated by implantation of parasite stages into inbred mice. Adherent peritoneal exudate cells (PEC) from mice transplanted with adult or larval Brugia malayi parasites are profoundly anti-proliferative but do not prevent antigen-specific cytokine production by T cells. We demonstrate here that the excretory/secretory (E/S) products of the adult parasite are sufficient to induce PEC that block proliferation if injected daily into mice. We have previously shown that in vivo production of host IL-4 is required for the generation of suppressive cells. Because the induction of host IL-4 is characteristic of infection with nematodes, we asked whether E/S from two other nematode parasites, Nippostrongylus braziliensis and Toxocara canis were also capable of generating a suppressor cell population. Injection of E/S from these two parasites also led to a reduction in T cell proliferation suggesting that this mechanism of down-regulating host responses is a feature common to nematode parasites.