Cutting Edge: CD4+CD25+ Alloantigen-Specific Immunoregulatory Cells That Can Prevent CD8+ T Cell-Mediated Graft Rejection: Implications for Anti-CD154 Immunotherapy

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Abstract
Blockade of CD40-CD154 interactions can facilitate long-term allograft acceptance in selected rodent and in primate models, but, due to the ability of CD154-independent CD8+ T cells to initiate graft rejection, this strategy is not always effective. In this work we demonstrate that blockade of the CD40-CD154 pathway at the time of transplantation enables the generation of donor alloantigen-specific CD4+CD25+ regulatory T cells, and that if the regulatory cells are present in sufficient numbers they can suppress allograft rejection mediated by CD154-independent CD8+ T cells.