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. 1992 Aug 7;257(5071):789-92.
doi: 10.1126/science.1323143.

Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg

D J Lenschow  1 , Y Zeng, J R Thistlethwaite, A Montag, W Brady, M G Gibson, P S Linsley, J A Bluestone
Affiliations

Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg

D J Lenschow et al. Science. .

Abstract

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.

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