Interferon γ-independent effects of interleukin 12 administered during acute or established infection due to Leishmania major

Zhi En Wang, Shichun Zheng, David B. Corry, Dyana K. Dalton, Robert A. Seder, Steven L. Reiner, Richard M. Locksley

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells, their generation of interferon γ (IFN-γ), and the differentiation of T helper type 1 (T(h1)) effector cells from naive precursors in vitro. These activities are consistent with the capacity of exogenous IL-12 to heal otherwise susceptible BALB/c mice infected with the intramacrophage parasite Leishmania major. Using this characterized model of CD4 cell subset differentiation, we examined the immunologic effects of IL- 12 administered either at the time of infection, when naive T cells are primed, or after 14 days of infection, by which time CD4+ subset differentiation has occurred. Given with the inoculation of parasites, IL-12 induced IFN-γ and IL-10 and markedly suppressed IL-4. Effects on IL-10 and IL-4 were comparable in mice with homozygous disruption of the IFN-γ gene (IFN-γ(0/0)), and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10 antibody. Induction of IFN-γ and IL-10 mRNA by IL- 12 also occurred in infected SCID mice. Given after day 14 of infection, however, IL-12 not only induced IFN-γ and IL-10 but also induced IL-4 in normal and IFN-γ(0/0) mice. These data demonstrate direct effects of IL-12 independent of IFN-γ, IL-10, and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with L. major correlates with resistance of differentiated T(h2) cells to the IL-4- suppressing activity of IL-12.

Original languageEnglish (US)
Pages (from-to)12932-12936
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number26
DOIs
StatePublished - Dec 20 1994

Keywords

  • cell-mediated immunity
  • cytokines
  • interleukin 4
  • leishmaniasis

ASJC Scopus subject areas

  • Genetics
  • General

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