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Significant enhancement by anti‐ICOS antibody of suboptimal tacrolimus immunosuppression in rat liver transplantation
Author(s) -
Guo Lei,
Li XiaoKang,
Enosawa Shin,
Funeshima Naoko,
Suzuki Seiichi,
Kimura Hiromitsu,
Sugawara Yasuhiko,
Tezuka Katsunari,
Makuuchi Masatoshi
Publication year - 2004
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.20167
Subject(s) - immunosuppression , tacrolimus , medicine , liver transplantation , antibody , donor specific antibodies , graft rejection , transplantation , immunology , kidney transplantation
A member of the costimulatory molecule family, inducible costimulator (ICOS), is expressed on activated T cells and plays a critical role in their primary activation and cytokine production. ICOS is involved in different immune phenomena, such as Th1‐mediated autoimmune disease and graft rejection. Although blockade of ICOS costimulation theoretically may protect grafts from rejection, a single dose of anti‐ICOS antibody did not result in the prolongation of rat liver allograft survival. However, in this article, we report that anti‐rat ICOS antibody markedly enhanced the immunosuppressive activity of a suboptimal dose of tacrolimus (FK506). After fully allogenic DA to LEW liver transplantation, recipients received a single injection of tacrolimus (1 mg/kg, intramuscularly) with or without anti‐ICOS antibody (1 mg/kg, intravenously). Recipient survival was significantly prolonged in rats treated with both the antibody and suboptimal tacrolimus (median survival time 44 days vs. 28 days with tacrolimus alone, P < .01). The extent of cell infiltration into the graft was closely associated with prolongation of recipient survival. Our findings thus demonstrate that anti‐ICOS antibody immunotherapy combined with suboptimal tacrolimus has a synergistic effect in preventing hepatic allograft rejection and that it may induce long‐term graft acceptance intimately associated with a marked reduction of intragraft T lymphocyte infiltration. (Liver Transpl 2004;10:743–747.)