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IL-12 is both required and prognostic in vivo for T helper type 1 differentiation in murine candidiasis.

L Romani, A Mencacci, L Tonnetti, R Spaccapelo, E Cenci, P Puccetti, S F Wolf and F Bistoni
J Immunol December 1, 1994, 153 (11) 5167-5175;
L Romani
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A Mencacci
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L Tonnetti
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R Spaccapelo
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E Cenci
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P Puccetti
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S F Wolf
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F Bistoni
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Abstract

In murine models of systemic candidiasis, healing and nonhealing patterns of disease are associated with preferential expansion of Th1 and Th2 cells, respectively. As previous studies have shown IL-12 to be expressed transcriptionally in healer mice and to be required for Th1 development in vitro, this cytokine might play a role in Candida-driven Th1 cell differentiation in vivo. In the present study, IL-12-neutralizing Abs or recombinant IL-12 were administered to mice with healing or progressive candidiasis, respectively, and the animals were monitored for mortality, resistance to reinfection, serum levels of specific Abs, and IFN-gamma, IL-4, and IL-10 message/protein expression by CD4+ cells. In self-limiting infection by a yeast vaccine strain, neutralization of IL-12 ablated development of acquired anticandidal resistance and led to appearance of Candida-specific IgE and IL-4-producing cells. In mice with progressive systemic disease as well as in a mucosal infection model, administration of IL-12 did not result in therapeutic activity under conditions of yeast infection that would instead be resolved by serologic ablation of IL-4 or IL-10. Yet, in systemically infected mice cured by anti-IL-4 or anti-IL-10 therapy, the emergence of a Th1 response correlated with the detection of high levels of circulating IL-12 and splenic IL-12 transcripts. Although exogenous IL-12 may not be sufficient for Th conversion in the presence of an overwhelming IL-4/IL-10 response, endogenous production of IL-12 may be both required and prognostic for Th1 differentiation in vivo.

  • Copyright © 1994 by American Association of Immunologists

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The Journal of Immunology
Vol. 153, Issue 11
1 Dec 1994
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IL-12 is both required and prognostic in vivo for T helper type 1 differentiation in murine candidiasis.
L Romani, A Mencacci, L Tonnetti, R Spaccapelo, E Cenci, P Puccetti, S F Wolf, F Bistoni
The Journal of Immunology December 1, 1994, 153 (11) 5167-5175;

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IL-12 is both required and prognostic in vivo for T helper type 1 differentiation in murine candidiasis.
L Romani, A Mencacci, L Tonnetti, R Spaccapelo, E Cenci, P Puccetti, S F Wolf, F Bistoni
The Journal of Immunology December 1, 1994, 153 (11) 5167-5175;
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Print ISSN 0022-1767        Online ISSN 1550-6606