Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells

S. E. Macatonia, N. A. Hosken, M. Litton, P. Vieira, C. S. Hsieh, J. A. Culpepper, M. Wysocka, G. Trinchieri, K. M. Murphy, A. O'Garra

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Abstract

Dendritic cells are APCs that are unique in their potency to stimulate proliferation of primary Ag-specific responses in vitro and in vivo. In this study, we demonstrate that dendritic cells can produce IL-12, a dominant cytokine involved in the development of IFN-γ-producing T cells. This finding resulted from our observations that dendritic cell-induced Th1 development from total CD4+ T cells upon neutralization of endogenous levels of IL-4 was IL-12-dependent. Furthermore, we demonstrate that dendritic cells can induce the development of Th1 cells from Ag-specific naive LECAM- 1(bright) CD4+ T cells obtained from αβ-TCR transgenic mice, provided that CD4+ LECAM-1(dull) T cells, which produce significant levels of IL-4, are not present in the primary cultures. Production of IL-12 by dendritic cells was confirmed by positive immunofluorescence staining with Abs specific for the inducible IL-12 p40 subunit. This suggests that in addition to inducing proliferation and clonal expansion of naive T cells, dendritic cells, by their production of IL-12, play a direct role in the development of IFN-γ- producing cells that are important for cell-mediated immune responses.

Original languageEnglish
Pages (from-to)5071-5079
Number of pages9
JournalJournal of Immunology
Volume154
Issue number10
StatePublished - Jan 1 1995

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    Macatonia, S. E., Hosken, N. A., Litton, M., Vieira, P., Hsieh, C. S., Culpepper, J. A., Wysocka, M., Trinchieri, G., Murphy, K. M., & O'Garra, A. (1995). Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. Journal of Immunology, 154(10), 5071-5079.