REQUIREMENT FOR IN-VIVO PRODUCTION OF IL-4, BUT NOT IL-10, IN THE INDUCTION OF PROLIFERATIVE SUPPRESSION BY FILARIAL PARASITES (VOL 160, PG1304, 1998)

Loss of T lymphocyte proliferation and the emergence of a host respons e that is dominated by a Th2-type profile are well-established feature s of human filariasis, We have previously: reported that adherent peri toneal exudate cells (PEG) from mice transplanted with adult Brugia ma layi parasites suppress the proliferation of lymphocytes without block ing Ag-cytokine production in vitro, We now show that infection of mic e with the infective larval (L3) stage of B, malayi generates a simila r 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 prod uction 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 implante d with adult parasites resulted in T cell suppression, indicating that IL-10 is not essential for the induction of hyporesponsiveness. Neith er IL-3 nor IL-10 were directly responsible for ablating cellular prol iferation in vitro, as the addition of neutralizing Ab to either cytok ine did not reverse the proliferative block, Thus, IL-4 produced in vi vo in response to filarial L3 and adult parasites is essential for the induction of proliferative suppression but is not itself the suppress ive factor.