Transforming growth factor beta decreases the immunogenicity of rat islet xenografts (rat to mouse) and prevents rejection in association with treatment of the recipient with a monoclonal antibody to interferon gamma.
Culture of rat islets of Langerhans for 1 week at 37 degrees C with recombinant transforming growth factor beta prolonged the survival of islet xenografts transplanted into diabetic mouse recipients. Treatment of diabetic recipients with a neutralizing monoclonal antibody to murine interferon gamma did not affect the survival of islet xenografts cultured 7 days in control medium. However, treatment of donor islets with transforming growth factor beta in combination with treatment of diabetic recipients with interferon gamma antibody produced a 75% survival of the islet xenografts at 100 days. Fifty percent of the recipients who had accepted their graft for more than 100 days were immune unresponsive to a transplant of freshly isolated islets from the same donor strain.
Carel
J C
JC
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
Schreiber
R D
RD
Falqui
L
L
Lacy
P E
PE
D000818:Animals; D002478:Cells, Cultured; D006084:Graft Rejection / Q000187:drug effects*; D006085:Graft Survival / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007340:Insulinoma / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; D007371:Interferon-gamma