Dendritic cells require maturation via CD40 to generate protective antitumor immunity.
A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously. Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination. Furthermore, protective antitumor responses can be restored in CD40-deficient mice by the coadministration of CD40+/+ but not CD40-/- dendritic cells (DCs) with tumor Ag, suggesting that CD40 is critical for the maturation and function of DCs in vivo. Finally, we demonstrate that an IL-12-transduced but not a mock-transduced tumor vaccine induces systemic tumor immunity in anti-CD154-treated and CD154-deficient mice. These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.
Mackey
M F
MF
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Gunn
J R
JR
Maliszewsky
C
C
Kikutani
H
H
Noelle
R J
RJ
Barth
R J
RJ
D000818:Animals; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D007116:Immunization, Passive / Q000379:methods; D018664:Interleukin-12 / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012513:Sarcoma, Experimental / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12