Invited lecture: Expression of IDO in human mature dendritic cells in vivo
(2009) 2nd International IDO Meeting — Location: Bonn, Germany (13.May.2009)
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- Abstract
- Indoleamine dioxygenase (IDO) is a tryptophan-degrading enzyme that contributes to peripheral tolerance by inducing a local tryptophan shortage that prevents T cell proliferation. We studied the expression of IDO in human normal tissues by immunohistochemistry using a novel monoclonal antibody we raised against human IDO. Most normal tissues were completely negative, with the exception of lymphoid tissues, which contained scattered IDO-positive cells located in T cell areas of normal lymph nodes, in the spleen, the gut lamina propria and the thymus. Their morphology corresponded to that of interdigitating dendritic cells. Using a novel virtual double staining technique, we identified those IDO-positive cells in lymph nodes as mature dendritic cells (DC), based on their expression of CD83 and DC-Lamp and their lack of expression of macrophage marker CD163. Surprisingly, they did not express CD123, a marker of plasmacytoid dendritic cells, which have been claimed to express IDO. IDO-expressing DC represented about 50% of mature DC in the lymph nodes. Tumor-draining lymph nodes were reported to been enriched in IDO-positive dendritic cells. Since the published data were obtained using polyclonal antibodies that were cross-reactive, we evaluated the expression of IDO in tumor-draining lymph nodes, using our specific monoclonal antibody on a similar series of clinical samples from breast carcinomas and melanomas. We found IDO-positive dendritic cells in those tumor-draining lymph nodes. However, their frequency and phenotype were identical to those observed in normal lymph nodes. We then evaluated the expression of IDO in monocyte-derived dendritic cells obtained in vitro with GM-CSF and IL-4. Immature dendritic cells did not express IDO, while IDO expression was induced upon maturation. The strongest maturation stimuli also induced the strongest IDO expression. This IDO was enzymatically active, and caused a reduction of allogeneic T cell proliferation observed in medium conditioned by mature DCs.
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Van den Eynde, B., Théate, I., Moulin, P., Nizet, Y., Renauld, J.-C., Larrieu, P., Hervé, C., & Pilotte, L. (2009). Invited lecture: Expression of IDO in human mature dendritic cells in vivo. 2nd International IDO Meeting, Bonn, Germany. https://hdl.handle.net/2078.5/48455