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CUTTING EDGE |
*
Laboratory of Experimental Immunology, Free University of Brussels, Brussels, Belgium;
Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium;
Animal Research Center, Institute of Medical Science, University of Tokyo, Japan
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-
, and decreased IL-4
production by donor-specific T cells in vitro. Experiments using
anti-cytokine mAb and IFN--deficient mice demonstrated that CD40
ligation prevents neonatal allotolerance through an IFN-- 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.
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