Science, Vol 257, Issue 5071, 789-792
Copyright © 1992 by American Association for the Advancement of Science
Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg
DJ Lenschow,
Y Zeng,
Thistlethwaite JR,
A Montag,
W Brady,
MG Gibson,
PS Linsley,
and
JA Bluestone
Ben May Institute, University of Chicago, IL 60637.
Antigen-specific T cell activation depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (lg) G1 Fc region (CTLA4lg) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4lg therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells. In addition, CTLA4lg induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.
