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CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion.

Silke Gillessen·Yuri N Naumov·Edward E S Nieuwenhuis·Mark A Exley·Frederick S Lee·Nicolas Mach·Andrew D Luster·Richard S Blumberg·Masaru Taniguchi·Steven P Balk·Jack L Strominger·Glenn Dranoff·S Brian Wilson
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Abstract

CD1d-restricted T cells contribute to tumor protection, but their precise roles remain unclear. Here we show that tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor induce the expansion of CD1d-restricted T cells through a mechanism that involves CD1d and macrophage inflammatory protein 2 expression by CD8 alpha-, CD11c+ dendritic cells (DCs). The antitumor immunity stimulated by vaccination with irradiated, granulocyte-macrophage colony-stimulating factor-secreting tumor cells was abrogated in CD1d- and J alpha 281-deficient mice, revealing a critical role for CD1d-restricted T cells in this response. The loss of antitumor immunity was associated with impaired tumor-induced T helper 2 cytokine production, although IFN-gamma secretion and cytotoxicity were preserved. DCs from immunized CD1d-deficient mice showed compromised maturation and function. Together, these results delineate a role for CD1d-restricted T cell-DC cross talk in the shaping of antitumor immunity.

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AnimalsAntigens, CD1Antigens, CD1dCancer VaccinesChemokine CXCL2ChemokinesDendritic CellsFemaleGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorImmunity, CellularIn Vitro TechniquesKiller Cells, NaturalMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutT-Lymphocyte SubsetsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Silke Gillessen, Yuri N Naumov, Edward E S Nieuwenhuis, Mark A Exley, Frederick S Lee, Nicolas Mach, Andrew D Luster, Richard S Blumberg, Masaru Taniguchi, Steven P Balk, Jack L Strominger, Glenn Dranoff, S Brian Wilson. 2003-07-07. CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion.. https://doi.org/10.1073/pnas.1033098100

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