STAGE-SPECIFIC INDUCTION OF CYTOKINES REGULATES THE IMMUNE-RESPONSE IN LYMPHATIC FILARIASIS

Parasite stage-specific T cell responses were studied in Indians with lymphatic filariasis manifesting as elephantiasis (CP, n = 11) and asy mptomatic microfilaremia (MF, II = 8), using antigens derived from the microfilarial, adult male only, and mixed adult male and female worms . Proliferative responses to microfilarial and mixed (male-female adul t worm) antigens in MF individuals were markedly impaired compared to corresponding responses in individuals with CP. In contrast, T cell pr oliferative responses to adult male-derived antigens were not statisti cally different between the two groups. Analysis of antigen driven cyt okine secretion by peripheral blood mononuclear cells from MF and CP i ndividuals revealed significantly lower IL-2 and IFN-gamma production by MF in response to microfilarial and mixed antigens (but not to adul t male antigen) compared to CP individuals. No differences were observ ed between MF and CP in parasite antigen-driven IL-4 or IL-5 productio n. Spontaneous and parasite-specific IL-10 secretion was also measured to determine if cytokine cross-regulation of Th1 responses may be a m echanism underlying the observed Th1 suppression. Spontaneous and micr ofilarial antigen-driven IL-10 was found to be significantly higher in MF than in CP individuals. These data indicate that MF individuals ex hibit preferentially impaired Th1-type responses to microfilarial anti gens and that microfilarial-induced IL-10 may be critical in the downr egulation of specific Th1 responses. (C) 1996 Academic Press, Inc.