CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion.
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.
Gillessen
Silke
S
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Naumov
Yuri N
YN
Nieuwenhuis
Edward E S
EE
Exley
Mark A
MA
Lee
Frederick S
FS
Mach
Nicolas
N
Luster
Andrew D
AD
Blumberg
Richard S
RS
Taniguchi
Masaru
M
Balk
Steven P
SP
Strominger
Jack L
JL
Dranoff
Glenn
G
Wilson
S Brian
SB
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*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D019496:Cancer Vaccines; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor