INFECTION OF IL-4-DEFICIENT MICE WITH THE PARASITIC NEMATODE BRUGIA-MALAYI DEMONSTRATES THAT HOST-RESISTANCE IS NOT DEPENDENT ON A T-HELPER2-DOMINATED IMMUNE-RESPONSE

Resistance of intact mice to infection with the filarial nematode, Bru gia malayi is dependent on the presence of T cells. To investigate the role of Th2 cells in this protection, mice with a targeted disruption of the IL-4 gene were infected with different developmental stages of B. malayi. We examined the phenotypic changes in the immune response and the survival of each stage in these mice. In wild-type mice, adult female worms induce Th2 responses, characterized by antigen-specific IgG1 production, elevated IgE, and marked IL-4 secretion by splenocyte s stimulated in vitro with Brugia extract. However, first stage larvae (microfilariae), induce Th1 responses with the appearance of antigen- specific IgG2a, IgG2b, and IgG3 and IFN-gamma secretion by splenocytes . infection of IL-4-deficient mice revealed a dramatic change in the r esponse to adult worms, with a severe reduction in IgG1 production and a corresponding increase in the production of IgG2a, IgG2b, IgG3, and IFN-gamma release. The switch to Th1-type responses was particularly marked in IL-4-deficient recipients of female worms, which continually release live microfilariae. In the absence of IL-4, down-regulation o f the microfilarial-induced Th1 response does not occur. Despite these profound alterations to the immune response in IL-4-deficient mice, s urvival of infective larvae, adult worms, or microfilariae in the peri toneal cavity was unaffected. In mice, therefore, the prominent Th2-ty pe response elicited by filarial parasites may not be an essential com ponent of the host protective immune response.