Immune responses to third stage larvae of Onchocerca volvulus in interferon-gamma and interleukin-4 knockout mice

To shed clarity on the dichotomy of reported results relative to the signif icance of T helper-1 vs T helper-2 immune responses in onchocerciasis, we c ompared the survivability of Onchocerca volvulus third-stage larvae (L3) in immunized mice that had either a targeted disruption of the Interleukin-4 or Interferon-gamma gene. Treatment groups consisted of control mice and mi ce immunized with irradiated O. volvulus L3. All mice were challenged with diffusion chambers containing viable L3. Vaccinated IL-4(-/-) were unable t o kill this larval target. In contrast vaccinated IFN-gamma(-/-) and C57BL/ 6 mice, exhibited high levels of killing, had elevated levels of IL-4 and s ignificantly greater,numbers of eosinophils in their diffusion chambers tha n the IL-4(-/-). Whereas, levels of IFN-gamma in all three groups of immuni zed mice were equivalent to those of control mice, levels of IL-5 were elev ated, even in the IL-4(-/-), indicating that cytokines other than IL-4 were involved in its production. The protective immune response to third-stage larvae of O. volvulus in mice vaccinated with irradiated larvae has an abso lute IL-4 requirement.