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  • Significant enhancement by anti-ICOS antibody of suboptimal tacrolimus immunosuppression in rat liver transplantation.

Significant enhancement by anti-ICOS antibody of suboptimal tacrolimus immunosuppression in rat liver transplantation.

Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (2004-05-27)
Lei Guo, Xiao-Kang Li, Shin Enosawa, Naoko Funeshima, Seiichi Suzuki, Hiromitsu Kimura, Yasuhiko Sugawara, Katsunari Tezuka, Masatoshi Makuuchi
ABSTRACT

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.

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Anti-Mouse IgG (whole molecule)−Alkaline Phosphatase antibody produced in goat, affinity isolated antibody, buffered aqueous glycerol solution