Document 0090
 DOCN  M9580090
 TI    IL-12 is required for natural killer cell activation and subsequent T
       helper 1 cell development in experimental leishmaniasis.
 DT    9506
 AU    Scharton-Kersten T; Afonso LC; Wysocka M; Trinchieri G; Scott P;
       Department of Pathobiology, University of Pennsylvania, School of;
       Veterinary Medicine, Philadelphia 19104, USA.
 SO    J Immunol. 1995 May 15;154(10):5320-30. Unique Identifier : AIDSLINE
       MED/95248098
 AB    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.
 DE    Animal  Antigens, Protozoan/IMMUNOLOGY  Cells, Cultured
       Cytokines/BIOSYNTHESIS/PHYSIOLOGY  Female  Interferon Type
       II/*BIOSYNTHESIS  Interleukin-12/BIOSYNTHESIS/*PHYSIOLOGY  Killer Cells,
       Natural/*IMMUNOLOGY  Leishmania major/IMMUNOLOGY
       Leishmaniasis/*IMMUNOLOGY/PATHOLOGY  Leishmaniasis, Cutaneous/IMMUNOLOGY
       Mice  Mice, Inbred BALB C  Mice, Inbred C3H  Mice, Inbred C57BL
       Spleen/CYTOLOGY  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       Th1 Cells/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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