Requirement for in vivo production of IL-4, but not IL-10, in the induction of proliferative suppression by filarial parasites (vol 160, pg 1304, 1998)

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 filariasis, We have previously: reported that adherent peritoneal exudate cells (PEG) from mice transplanted with adult Brugia malayi parasites suppress the proliferation of lymphocytes without blocking Ag-cytokine production in vitro, We now show that infection of mice with the infective larval (L3) stage of B, malayi generates a similar population of PEG. Suppressive cells are generated within 7 days of infection and mediate their effects through a nitric oxide-independent pathway, Both L3 and adult infection elicit high levels of host IL-4 whereas the microfilarial stage of the parasite induces IFN-gamma production and does not generate a similar form of suppression, Production of host IL-4 was necessary to allow the generation of suppressive PEG, given that IL-4-deficient mice implanted with adult parasites failed to induce proliferative block, However, IL-10-deficient mice implanted with adult parasites resulted in T cell suppression, indicating that IL-10 is not essential for the induction of hyporesponsiveness. Neither IL-3 nor IL-10 were directly responsible for ablating cellular proliferation in vitro, as the addition of neutralizing Ab to either cytokine did not reverse the proliferative block, Thus, IL-4 produced in vivo in response to filarial L3 and adult parasites is essential for the induction of proliferative suppression but is not itself the suppressive factor.