Nature Immunology3, 1097 - 1101 (2002)
Published online: 30 September 2002; | doi:10.1038/ni846
CTLA-4−Ig regulates tryptophan catabolism in vivo
Ursula Grohmann1, Ciriana Orabona1, 3, Francesca Fallarino1, 3, Carmine Vacca1, Filippo Calcinaro2, Alberto Falorni2, Paola Candeloro2, Maria L. Belladonna1, Roberta Bianchi1, Maria C. Fioretti1
& Paolo Puccetti1
1
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy.
2
Department of Internal Medicine, University of Perugia, 06126 Perugia, Italy.
3
These authors contributed equally to this work.
Correspondence should be addressed to Ursula Grohmann ugrohmann@tin.it
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.
