Affiliation:
1. Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104, USA.
Abstract
Abstract
Infection of mice with the protozoan Leishmania major is an established in vivo model for the definition of factors that contribute to CD4+ T helper cell subset development. In the current study, a central role for IL-12 in directing both the innate and adaptive immune responses to L. major is established. We show that in vivo neutralization of IL-12 eliminates the NK cell cytotoxic response and IFN-gamma production by lymph node cells from 2-day L. major-infected C3H mice. Moreover, anti-IL-12 treatment abrogated Th1 cell development and enhanced Th2 cell development. Consistent with these results, elevated IL-12 p40 production and an increase in the number of IL-12 p40-producing cells were observed within 1 day of infection in C3H mice. Because BALB/c mice lack an early NK cell response or a Th1-type immune response after L. major infection, we investigated the possibility that they had a defect in the ability to produce IL-12. Surprisingly, L. major infection stimulated IL-12 p40 production in BALB/c mice early after infection. Further studies suggest that BALB/c mice are unable to generate an early IFN-gamma response because of the simultaneous production of IL-12 and cytokines that inhibit IL-12 function, such as TGF-beta, IL-4, and IL-10. Together, these data show that IL-12 regulates the immune response to L. major, but that even when IL-12 is induced, Th1 cell development may be interrupted by simultaneous production of inhibitory cytokines.
Publisher
The American Association of Immunologists
Subject
Immunology,Immunology and Allergy
Cited by
26 articles.
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