TY - JOUR
T1 - Interferon γ-independent effects of interleukin 12 administered during acute or established infection due to Leishmania major
AU - Wang, Zhi En
AU - Zheng, Shichun
AU - Corry, David B.
AU - Dalton, Dyana K.
AU - Seder, Robert A.
AU - Reiner, Steven L.
AU - Locksley, Richard M.
PY - 1994/12/20
Y1 - 1994/12/20
N2 - 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.
AB - 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.
KW - cell-mediated immunity
KW - cytokines
KW - interleukin 4
KW - leishmaniasis
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U2 - 10.1073/pnas.91.26.12932
DO - 10.1073/pnas.91.26.12932
M3 - Article
C2 - 7809149
AN - SCOPUS:0028670487
SN - 0027-8424
VL - 91
SP - 12932
EP - 12936
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -