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  • Title: Early T cell unresponsiveness in mice with candidiasis and reversal by IL-2: effect on T helper cell development.
    Author: Spaccapelo R, Del Sero G, Mosci P, Bistoni F, Romani L.
    Journal: J Immunol; 1997 Mar 01; 158(5):2294-302. PubMed ID: 9036977.
    Abstract:
    To investigate the role and effect of IL-2 in the genesis of Th1 and Th2 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 type of CD4+ Th immunity elicited. High levels of IL-2 production and Ag-specific proliferation in vitro correlated with disease progression in susceptible mice. In contrast, resolution of infection in resistant mice was accompanied by the induction of Ag-specific hyporesponsiveness and impaired IL-2 production. Progression of infection did not occur in susceptible mice treated with anti-IL-2 or anti-IL-2R mAbs; conversely, disease resolution was prevented in resistant mice treated with IL-2. CD4+ Th1 cell responses were present in BALB/c mice rendered resistant by IL-2 neutralization and CD4+ Th2 responses in mice rendered susceptible by IL-2 treatment. The presence of IL-2 restored Ag-specific responsiveness in vitro and correlated in vivo with the expansion of CD4+ MEL-149(low) cells capable of producing IL-2 and IL-4 both in vitro and in vivo as observed in adult thymectomized mice. These results indicate that production of IL-2 early in infection correlates with the induction of IL-4-producing CD4+ Th2 cells, while a transient loss of T cell responsiveness, such as IL-2 production, appears to be required for CD4+ Th1 occurrence in mice with candidiasis.
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