ADULT AND MICROFILARIAL STAGES OF THE FILARIAL PARASITE BRUGIA-MALAYISTIMULATE CONTRASTING CYTOKINE AND IG ISOTYPE RESPONSES IN BALB C MICE/

Natural infection with filarial nematode parasites shows many characte ristics of a Th2 immune response. In these infections, long-lived adul t worms inhabit the lymphatics, releasing larval microfilariae (Mf) in to the blood stream. To compare the effect of these different developm ental stages on the mammalian immune system, Mf and adult worms of eit her sex were implanted into BALB/c mice, in which they survive for at least 28 days. Serum Ab responses showed that whereas Mf stimulated sp ecific Abs of all IgG subclasses, but little total IgE, adult worms st imulated only IgG1 and IgE responses. Splenocytes from implanted mice were stimulated in vitro with specific Ag or Con A and assayed for pro liferation and profiles of cytokine secretion. Cells from Mf-infected mice secreted high levels of IFN-gamma (30 U/ml) throughout infection, but very little IL-4 at the early time points. By day 28 postinfectio n, however, splenocytes from Mf-infected mice showed some IL-4 secreti on in response to specific Ag (40 U/ml). The IFN-gamma response to Mf was found to be independent of the inoculum dose in the range of 10(2) to 10(6) organisms. In contrast, splenocytes taken from adult worm-im planted mice on days 14, 21, and 28 postinfection produced high levels of IL-4 (up to 435 U/ml) and negligible amounts of IFN-gamma despite the production of large numbers of Mf by adult female worms. CD4(+) ce lls were primarily responsible for this IL-4 production. These results demonstrate that adult filarial parasites, and females in particular, exert a rapid polarization of the immune response in a Th2-like direc tion, but that this effect may be modulated by the Mf stage.