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Medline ® Abstract for Reference 145

of 'Principles of cancer immunotherapy'

Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation.
Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA
J Immunol. 2000 Apr;164(7):3596-9.
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-gamma. 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-gamma. 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.
Surgery Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892, USA.