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 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 (PEC) 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 PEC. 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 PEC, 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-4 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.
MacDonald
A S
AS
Institute of Cell, Animal and Population Biology, University of Edinburgh, UK.
Maizels
R M
RM
Lawrence
R A
RA
Dransfield
I
I
Allen
J E
JE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000032:analysis; D001202:Ascitic Fluid / Q000166:cytology; D017178:Brugia malayi / Q000254:growth & development / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D005368:Filariasis / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D007814:Larva / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D000943:Antigens, Differentiation; D013491:Suppressor Factors, Immunologic; C036763:monocyte-macrophage differentiation antigen; D016753:Interleukin-10; D015847:Interleukin-4