To summarize the study performed in these 25 years at our department, following two topics, were introduced.

Abstract

1) Anergic T cells generated ex vivo are reported to have immunosuppressive effects in vitro and in vivo. Here, we tested this concept in nonhuman primates. Alloreactive T cells were rendered anergic ex vivo by coculture with donor alloantigen in the presence of anti-CD80/CD86 mAbs before adoptive transfer via renal allograft to rhesus monkey recipients. Rejec-tion-free survival was prolonged in all treated recipients, and 3 of 6 animals showed longterm survival (two years at study's end). We conclude that the anergic T cells generated can suppress renal allograft rejection after adoptive transfer in nonhuman primates. 2) Tumor-cell apoptosis is the basis of many cancer therapies, and tumor-specific T cells are the principal effectors of successful antitumor immunotherapies. Here we show that induction of tumor-cell apoptosis by an agonistic monoclonal antibody to DR5, the apoptosisinducing receptor for TNF-related apoptosis-inducing ligand (TRAIL), combined with T-cell activation by agonistic monoclonal antibodies to the costimulatory molecules CD40 and CD137, potently and rapidly atimulated tumor-specific effector CD8+T cells capable of eradicating preestablished tumors. These findings in mice indicate that a rational monoclonal antibody-based therapy that both causes tumor-cell apoptosis through DR5 and activates T cells may be an effective strategy for cancer immunotherapy in humans.