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Grohmann, Ursula; Orabona, Ciriana; Fallarino, Francesca; Vacca, Carmine; Calcinaro, Filippo; Falorni, Alberto; Candeloro, Paola; Belladonna, Maria L; Bianchi, Roberta; Fioretti, Maria C; Puccetti, Paolo
Nature immunology, 11/2002, Volume: 3, Issue: 11Journal Article
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a critical role in peripheral tolerance. However, regulatory pathways initiated by the interactions of CTLA-4 with B7 counterligands expressed on antigen-presenting cells are not completely understood. We show here that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4-immunoglobulin (CTLA-4-Ig) is contingent upon effective tryptophan catabolism in the host. In vitro, we show that CTLA-4-Ig regulates cytokine-dependent tryptophan catabolism in B7-expressing dendritic cells. These data suggest that modulation of tryptophan catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals.
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