Effect of mediators of innate immunity and inflammation on CD8+ veto cells.
BACKGROUND
Methods of allotolerance induction that are successful in mice often fail in primates. Activators of innate immunity derived from microbial pathogens, which are present in primate populations but not in pathogen-free mouse colonies, have been shown to overcome tolerance induction by co-stimulatory blockade or regulatory T cells. Unlike other strategies, veto cells promote long-term allograft survival in primates. Accordingly, the authors hypothesized that veto cells are resistant to the effects of innate immune activation.


METHODS
Using mixed lymphocyte reactions as a model of alloimmunization, the authors assessed the effect of inflammatory mediators on veto cell activity. RESULTS.: The authors demonstrate that the activity of veto cells is unaltered by lipopolysaccharide, double-stranded RNA, or interferon-gamma. Tumor necrosis factor-alpha modestly inhibited the veto effect, but only when veto cells were limiting.


CONCLUSIONS
These findings may help to explain why veto cell-based therapies are more effective than other approaches in primate populations.
Zimring
James C
JC
Transfusion Medicine Program, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Woodruff Memorial Building, Room 7301, 101 Woodruff Circle, Atlanta, GA 30322, USA. jzimrin@emory.edu
Chadwick
Traci E
TE
Hillyer
Christopher D
CD
Roback
John D
JD
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007108:Immune Tolerance; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012330:RNA, Double-Stranded / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma