EARLY T-CELL UNRESPONSIVENESS IN MICE WITH CANDIDIASIS AND REVERSAL BY IL-2 - EFFECT ON T-HELPER CELL-DEVELOPMENT

To investigate the role and effect of IL-2 in the genesis of Th1 and T h2 responses to Candida albicans in vivo, we assessed the levels of IL -2 production and the Ag-specific proliferative response in mice with healing or nonhealing infection and the effects of IL-2 neutralization or administration on the course and outcome of infection and on the t ype of CD4(+) Th immunity elicited. High levels of IL-2 production and Ag-specific proliferation in vitro correlated with disease progressio n in susceptible mice. In contrast, resolution of infection in resista nt mice was accompanied by the induction of Ag-specific hyporesponsive ness and impaired IL-2 production. Progression of infection did not oc cur in susceptible mice treated with anti-IL-2 or anti-IL-2R mAbs; con versely, disease resolution was prevented in resistant mice treated wi th IL-2. CD4(+) Th1 cell responses were present in BALB/c mice rendere d resistant by IL-2 neutralization and CD4(+) Th2 responses in mice re ndered susceptible by IL-2 treatment. The presence of IL-2 restored Ag -specific responsiveness in vitro and correlated in vivo with the expa nsion of CD4(+)MEL-14(low) cells capable of producing IL-2 and IL-4 bo th in vitro and in vivo as observed in adult thymectomized mice. These results indicate that production of IL-2 early in infection correlate s with the induction of IL-4-producing CD4(+) Th2 cells, while a trans ient loss of T cell responsiveness, such as IL-2 production, appears t o be required for CD4(+) Th1 occurrence in mice with candidiasis.