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 gamma (IFN-gamma) in vitro by splenic CD4+ lymphocytes, and levels of IL-4 and IFN-gamma 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-gamma-specific transcripts. Our data thus indicate that the production of IL-4 by Th2 cells may limit Th1-associated protective immunity in murine candidiasis.
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July 01 1992
Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis.
L Romani,
L Romani
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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A Mencacci,
A Mencacci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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U Grohmann,
U Grohmann
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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S Mocci,
S Mocci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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P Mosci,
P Mosci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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P Puccetti,
P Puccetti
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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F Bistoni
F Bistoni
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
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L Romani
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
A Mencacci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
U Grohmann
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
S Mocci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
P Mosci
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
P Puccetti
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
F Bistoni
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 176 (1): 19–25.
Citation
L Romani, A Mencacci, U Grohmann, S Mocci, P Mosci, P Puccetti, F Bistoni; Neutralizing antibody to interleukin 4 induces systemic protection and T helper type 1-associated immunity in murine candidiasis.. J Exp Med 1 July 1992; 176 (1): 19–25. doi: https://doi.org/10.1084/jem.176.1.19
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