The cytotoxic T lymphocyte–associated antigen 4–Ig prolongs allograft survival in several rodent models and in some instances can lead to tolerance induction, but the exact mechanisms involved have been unclear. In September 30
Grohmann et al. used chemically diabetic mice and observed that long-term survival of pancreatic islet allografts induced by the soluble fusion protein CTLA-4–Ig was dependent upon effective tryptophan catabolism in the host. In addition, they showed that in vitro CTLA-4–Ig regulates cytokine-dependent tryptophan catabolism in B7-expressing dendritic cells.
These results suggest that, "localized control of tryptophan catabolism in specific tissue microenvironments may contribute to the induction and maintenance of peripheral tolerance," conclude the authors.