A Regulatory Trio

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Science  17 Aug 2007:
Vol. 317, Issue 5840, pp. 873
DOI: 10.1126/science.317.5840.873b

Immune responses rely on many regulatory strands that may act independently or cooperatively. Madhav et al. provide evidence for the intersection of three prominent regulatory mechanisms in mice that develop in response to tumors. Their study builds on the previous identification of an immune-suppressive dendritic cell (DC) subset present in lymph nodes that drain from tumors. Although the potent tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) produced by these cells already has its own direct immune-suppressive credentials, it emerged that this source of IDO could rouse local regulatory T cells. These cells also possess their own direct suppressive activity, but in this case provided additional feedback on IDO-expressing DCs to induce the expression of the cell-surface protein PD-L1, which curbed the proliferation of T cells in culture. Blocking PD-L1 with antibodies or growing tumors in IDO-deficient mice interfered with the inhibitory activity exerted by regulatory T cells. This study raises the question of whether equivalent suppressive pathways induced by IDO-producing DCs and linked through the activity of regulatory T cells might also develop in response to tumors in humans. — SJS

J. Clin. Invest. 117, 10.1172/JCI31911 (2007).

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