CTLA-4–Ig regulates tryptophan catabolism in vivo

U Grohmann, C Orabona, F Fallarino, C Vacca… - Nature …, 2002 - nature.com
U Grohmann, C Orabona, F Fallarino, C Vacca, F Calcinaro, A Falorni, P Candeloro…
Nature immunology, 2002nature.com
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 …
Abstract
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.
nature.com