Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation.
In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals. Here, we demonstrate that constitutive ligation of the tumor necrosis factor receptor family member CD27 by its ligand CD70 quantitatively augments CD8+ T cell responses to influenza virus infection and EL-4 tumor challenge in vivo by incrementing initial expansion and maintaining higher numbers of antigen-specific T cells in the memory phase. Concomitantly, the quality of antigen-specific T cells improved as evidenced by increased interferon (IFN)-gamma production and a greater cytotoxic potential on a per cell basis. As an apparent consequence, the superior effector T cell formation induced by CD70 protected against a lethal dose of poorly immunogenic EL4 tumor cells in a CD8+ T cell- and IFN-gamma-dependent manner. Thus, CD70 costimulation enhances both the expansion and per cell activity of antigen-specific CD8+ T cells.
Arens
Ramon
R
Laboratory for Experimental Immunology, Academic Medical Center, University of Amsterdam, Netherlands.
Schepers
Koen
K
Nolte
Martijn A
MA
van Oosterwijk
Michiel F
MF
van Lier
René A W
RA
Schumacher
Ton N M
TN
van Oers
Marinus H J
MH
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D053282:CD27 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D006084:Graft Rejection; D007371:Interferon-gamma / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
D015703:Antigens, CD; D053282:CD27 Ligand; C505772:Cd70 protein, mouse; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D007371:Interferon-gamma