Effect in vitro and in vivo of a rat anti-CD2 monoclonal antibody (LO-CD2b) on pig-to-baboon xenogeneic cellular (T and natural killer cells) immune response

Although hyperacute rejection of discordant xenogeneic grafts can be preven ted, baboon or human anti-pig cellular response may lead to acute xenograft rejection. Among the immune cellular actors participating in such a xenogr aft rejection are both T and natural killer (NK) cells. In the pre-clinical model of pig-to-baboon discordant xenograft, there is however, a lack of s pecific immunological therapeutic agent, in particular antibaboon T-cell mo noclonal antibodies do not exist. We therefore developed a rat anti-CD2 mon oclonal antibody (LO-CD2b) that recognizes both baboon and human CD2+ cells . In this study, we show that in vitro LO-CD2b inhibits a pig-to-baboon mix ed lymphocyte reaction, the direct cytotoxicity of baboon peripheral blood lymphocytes to pig aortic endothelial cells, as well as the baboon NK activ ity against K562 cell line. In vivo, LO-CD2b produces a strong depletion of all peripheral CD2+ cells including NK CD2+ cells. In summary, LO-CD2b rep resents an important immunological tool that can be used in the preclinical model of discordant pig-to-baboon vascularized xenograft.