Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg.
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.
Lenschow
D J
DJ
Ben May Institute, University of Chicago, IL 60637.
Zeng
Y
Y
Thistlethwaite
J R
JR
Montag
A
A
Brady
W
W
Gibson
M G
MG
Linsley
P S
PS
Bluestone
J A
JA
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival / Q000276:immunology* / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D010710:Phosphates / Q000032:analysis / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000502:physiology; D014501:Uranium / Q000032:analysis / Q000378:metabolism*; D017974:Uranium Compounds
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D010710:Phosphates; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D017974:Uranium Compounds; C075963:hydrogen uranyl phosphate; D014501:Uranium; D000069594:Abatacept