title: CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
authors.forename: Yuri N
authors.initials: YN
authors.lastname: Naumov
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.forename: Mark A
authors.initials: MA
authors.lastname: Exley
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Lee
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mach
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Steven P
authors.initials: SP
authors.lastname: Balk
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
authors.forename: S Brian
authors.initials: SB
authors.lastname: Wilson
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D019496:Cancer Vaccines; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor