Article: article from journal or magazin.
Early production of IL-4 in susceptible mice infected with Leishmania major rapidly induces IL-12 unresponsiveness.
Journal of Immunology
Previous results have documented a burst of IL-4 mRNA that peaks in draining lymph nodes of susceptible BALB/c mice 16 h after infection with Leishmania major. The importance of this early IL-4 response in subsequent Th2 cell maturation is supported by observations showing that 1) neutralization of IL-4 at the initiation of infection or 2) administration of IL-12, which results in an inhibition of the 16 h IL-4 mRNA burst, inhibits Th2 cell development. However, both treatments are effective in hampering Th2 cell development only if given at a time when IL-4 has been produced for <48 h. At this time after infection, lymph node CD4+ T cells from BALB/c mice no longer respond to IL-12. This IL-12 unresponsiveness is prevented in mice treated with anti-IL-4 Abs at the initiation of infection. Finally, the inhibition of Th2 development in BALB/c mice treated with anti-IL-4 Abs at the onset of infection results from maintenance of IL-12 responsiveness, since it requires IL-12. Together, these results reveal a narrow window of time, between 16 h and <48 h after infection, during which IL-4 produced rapidly in BALB/c mice renders T cells unresponsive to IL-12, allowing their differentiation toward the Th2 phenotype.
Animals, Antibodies, Monoclonal/pharmacology, Disease Susceptibility, Female, Immunity, Innate, Interleukin-12/biosynthesis, Interleukin-12/pharmacology, Interleukin-4/biosynthesis, Interleukin-4/genetics, Kinetics, Leishmania major/immunology, Leishmaniasis, Cutaneous/etiology, Leishmaniasis, Cutaneous/genetics, Lymph Nodes/cytology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Messenger/biosynthesis
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