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

S Gillessen, YN Naumov… - Proceedings of the …, 2003 - National Acad Sciences
S Gillessen, YN Naumov, EES Nieuwenhuis, MA Exley, FS Lee, N Mach, AD Luster…
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 CD8α–, CD11c+
dendritic cells (DCs). The antitumor immunity stimulated by vaccination with irradiated,
granulocyte-macrophage colony-stimulating factor-secreting tumor cells was abrogated in …
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 CD8α, 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 Jα281-deficient mice, revealing a critical role for CD1d-restricted T cells in this response. The loss of antitumor immunity was associated with impaired tumorinduced T helper 2 cytokine production, although IFN-γ 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.
National Acad Sciences