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*
Surgery Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892;
Department of Biology, Indiana University, Bloomington, IN 47405; and
National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
Dendritic cells (DCs) play a key role in the activation
and regulation of B and T lymphocytes. Production of indoleamine
2,3-dioxygenase (IDO) by macrophages has recently been described to
result in inhibition of T cell proliferation through tryptophan
degradation. Since DCs can be derived from monocytes, we sought to
determine whether DCs could produce IDO which could potentially
regulate T cell proliferation. Northern blot analysis of RNA from
cultured monocyte-derived human DC revealed that IDO mRNA was induced
upon activation with CD40 ligand and IFN-
. IDO produced from
activated DCs was functionally active and capable of metabolizing
tryptophan to kynurenine. Activated T cells were also capable of
inducing IDO production by DCs, which was inhibited by a neutralizing
Ab against IFN-. DC production of IDO resulted in inhibition of T
cell proliferation, which could be prevented using the IDO inhibitor
1-methyl-DL-tryptophan. These results suggest that
activation of DCs induces the production of functional IDO, which
causes depletion of tryptophan and subsequent inhibition of T cell
proliferation. This may represent a potential mechanism for DCs to
regulate the immune response.
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U. Grohmann, F. Fallarino, R. Bianchi, M. L. Belladonna, C. Vacca, C. Orabona, C. Uyttenhove, M. C. Fioretti, and P. Puccetti IL-6 Inhibits the Tolerogenic Function of CD8{{alpha}}+ Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase J. Immunol., July 15, 2001; 167(2): 708 - 714. [Abstract] [Full Text] [PDF]
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U. Grohmann, F. Fallarino, S. Silla, R. Bianchi, M. L. Belladonna, C. Vacca, A. Micheletti, M. C. Fioretti, and P. Puccetti CD40 Ligation Ablates the Tolerogenic Potential of Lymphoid Dendritic Cells J. Immunol., January 1, 2001; 166(1): 277 - 283. [Abstract] [Full Text] [PDF]
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E. Apolloni, V. Bronte, A. Mazzoni, P. Serafini, A. Cabrelle, D. M. Segal, H. A. Young, and P. Zanovello Immortalized Myeloid Suppressor Cells Trigger Apoptosis in Antigen-Activated T Lymphocytes J. Immunol., December 15, 2000; 165(12): 6723 - 6730. [Abstract] [Full Text] [PDF]
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