Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis

Abstract

An interleukin 4 (IL-4)-specific monoclonal antibody (mAb) was administered to mice infected systemically with the yeast Candida albicans, and the animals were monitored for mortality, development of delayed-type hypersensitivity, production of antibodies of different isotypes, release of IL-2, IL-4, IL-6, and interferon γ (IFN-γ) in vitro by splenic CD4+ lymphocytes, and levels of IL-4 and IFN-γ mRNA in these cells. Neutralization of IL-4 by three weekly injections of mAb in several independent experiments resulted in an overall cure rate of 81% versus 0% of controls. Cure was associated with efficient clearance of the yeast from infected organs and histologic evidence of disease resolution, detection of strong T helper type 1 (Th1) responses, and establishment of long-lasting protective immunity. Soon after infection, and as a result of the first or second injection of mAb, there was a decrease in IL-4 mRNA in CD4+ cells, which was accompanied by an increase in the levels of IFN-γ-specific transcripts. Our data thus indicate that the production of IL-4 by Th2 cells may limit Thl-associated protective immunity in murine candidiasis.