ENDOGENOUS INTERLEUKIN-4 IS REQUIRED FOR DEVELOPMENT OF PROTECTIVE CD4(-HELPER TYPE-1 CELL RESPONSES TO CANDIDA-ALBICANS() T)

Interleukin (IL)-4-deficient mice were used to assess susceptibility t o systemic or gastrointestinal Candida albicans infections, as well as parameters of innate and elicited T helper immunity. In the early sta ge of systemic infection with virulent C. albicans, an unopposed inter feron (IFN)-gamma response renders IL-4-deficient rmce more resistant than wild-type rmce to infection. Yet, IL-4-deficient mice failed to e fficiently control infection in the late stage and succumbed to it. De fective IFN-gamma and IL-12 production, but not IL-12 responsiveness, was observed in IL-4-deficient mice that failed to mount protective T helper type 1 cell (Th1)-mediated acquired immunity in response to a L ive vaccine strain of the yeast or upon mucosal immunization in vivo. In vitro, IL-4 primed neutrophils for cytokine release, including IL-1 2. However, late treatment with exogenous IL-4, while improving the ou tcome of infection, potentiated CD4(+) Th1 responses even in the absen ce of neutrophils. These findings indicate that endogenous IL-4 is req uired for the induction of CD4(+) Th1 protective antifungal responses, possibly through the combined activity on cells of the innate and ada ptive immune systems.