CD40 ligation prevents neonatal induction of transplantation tolerance.
To investigate the consequences of CD40 engagement on the neonatal induction of transplantation tolerance, BALB/c mice were injected at birth with (A/J x BALB/c) F1 spleen cells together with activating anti-CD40 mAb and grafted 4 wk later with A/J skin. Whereas A/J allografts were accepted in mice neonatally injected with F1 cells and control Ab, they were acutely rejected in mice injected with F1 cells and anti-CD40 mAb. Neonatal administration of anti-CD40 mAb resulted in enhanced anti-A/J CTL activity, increased IFN-gamma, and decreased IL-4 production by donor-specific T cells in vitro. Experiments using anti-cytokine mAb and IFN-gamma-deficient mice demonstrated that CD40 ligation prevents neonatal allotolerance through an IFN-gamma- and IL-12-dependent pathway. Finally, we found that newborn T cells express less CD40L than adult T cells upon TCR engagement. Taken together these data indicate that insufficiency of CD40/CD40L interactions contribute to neonatal transplantation tolerance.
Flamand
V
V
Laboratory of Experimental Immunology, Free University of Brussels, Belgium.
Donckier
V
V
Demoor
F X
FX
Le Moine
A
A
Matthys
P
P
Vanderhaeghen
M L
ML
Tagawa
Y
Y
Iwakura
Y
Y
Billiau
A
A
Abramowicz
D
D
Goldman
M
M
D000818:Animals; D000831:Animals, Newborn; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma