Broad antitumor protection by dendritic cells administered to CD8alpha knock out mice.
Dendritic cell (DC) administration to CD8alpha knock-out (CD8alphaKO) mice results in a strong antigen-non-specific protection to a B16 murine melanoma tumor challenge. This response is mediated by lytic NK cells and cytokine-producing CD4 cells. We aimed to determine the signals that guide tumor targeting of this response. CD8alphaKO mice in the C57BL/6 background received subcutaneous (s.c.) injections of immature DC. Mice were challenged in vivo or assayed for lytic activity in vitro to a panel of syngeneic tumors with different levels of MHC class I expression. These studies support the following conclusions: (1) DC administration to CD8alphaKO mice results in protective in vivo responses to syngeneic tumors from epithelial, neuroectodermal and hematopoietic origin; in vivo protection is independent of the level of MHC classes I and II expression. (2) The in vitro lytic activity of DC-activated NK cells from CD8alphaKO mice has sensitive and insensitive targets, which is independent of the cell lineage or the level of inhibitory self-MHC surface molecules. (3) In sensitive targets a putative activating NK ligand in DC-stimulated NK cells from CD8alphaKO mice signals directly to PI3-K, but is distinct from NKG2D.
Ribas
Antoni
A
Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, 90095, USA. aribas@mednet.ucla.edu
Vo
Dan D
DD
Weeks
David L
DL
Comin-Anduix
Begoña
B
Schumacher
Lana Y
LY
Garban
Hermes J
HJ
McLean
Colin
C
Yang
Jinquan
J
Dissette
Vivian B
VB
Peraza
Pedro
P
Owens
Sharla K
SK
McBride
William H
WH
Glaspy
John A
JA
Economou
James S
JS
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology
D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D019869:Phosphatidylinositol 3-Kinases