REQUIREMENT FOR IN-VIVO PRODUCTION OF IL-4, BUT NOT IL-10, IN THE INDUCTION OF PROLIFERATIVE SUPPRESSION BY FILARIAL PARASITES

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 perit oneal exudate cells (PEG) from mice transplanted with adult Brugia mal ayi parasites suppress the proliferation of lymphocytes without blocki ng 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 i nfection and mediate their effects through a nitric oxide-independent pathway. Both L3 and adult infection elicit high levels of host IL-4 w hereas the microfilarial stage of the parasite induces IFN-gamma produ ction 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-IO is not essential for the induction of hyporesponsiveness. Neithe r IL-4 nor IL-10 were directly responsible for ablating cellular proli feration in vitro, as the addition of neutralizing Ab to either cytoki ne did not reverse the proliferative block, Thus, IL-4 produced in viv o in response to filarial L3 and adult parasites is essential for the induction of proliferative suppression but is not itself the suppressi ve factor.