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Long‐Term Acceptance of Major Histocompatibility Complex‐Mismatched Cardiac Allograft Induced by a Low Dose of CTLA4IgM Plus FK506
Author(s) -
Yamada Akira,
Murakami Masaaki,
Ijima Kenichi,
Yagita Hideo,
Okumura Ko,
Komatsu Sakuzo,
Uede Toshimitsu
Publication year - 1996
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1996.tb01102.x
Subject(s) - major histocompatibility complex , fusion protein , immunology , transplantation , extracellular , medicine , biology , pharmacology , antigen , biochemistry , recombinant dna , gene
The immunosuppressant FK506 prolongs allograft survival. However, at therapeutic doses it has significant side effects. A fusion protein consisting of the extracellular portion of CTLA4 and the Fc portion of human IgG (CTLA4IgG) also prolongs allograft survival, but large doses of CTLA4IgG are required for the induction of cardiac allograft acceptance. Therefore, we constructed a pentameric form of a new CTLA4 fusion protein, CTLA4IgM. We tested whether low doses of CTLA4IgG or CTLA4IgM in combination with subtherapeutic doses of FK506 can prolong allograft survival in a synergistic fashion. C57BL/6 (H‐2 b ) neonatal hearts were transplanted to CBA/J (H‐2 k ) mice in a heterotopic, nonvascularized cardiac allograft model. The findings demonstrate that a combination of low doses of FK506 plus a pentameric form of CTLA4Ig, CTLA4IgM, leads to significant graft survival, while a combination of FK506 plus CTLA4IgG does not.