Effect of Sandimmun on Immune Response Development in Mice after Intraperitoneal and Intracerebral Introduction of Allogeneic Fetal Neural Cells

Abstract

The purpose of the study was to compare immune responces after intraperitoneal and intracerebral introduction of allogeneic fetal neural progenitor cells (NPCs) (Е13-15) and estimate the possibility of suppression of the arised immune response. Fetal NPC suspensions from donor CBA mice were intraperitoneally or intracerebrally introduced to recipient С57Bl/6 mice (1×10⁶ cells per animal). The part of animals underwent immunosuppression by Sandimmune (cyclosporin A for parenteral administration) in dose of 100 µg per animal on the 0th, 3rd, and 6th days. Intact animals served as the control. Alloimmune and antigenspecific responses were assessed on the 6th, 12th, 18th, and 37th day after cells introduction. Systemic (intraperitoneal) introduction of fetal NPCs caused more expressed cellular and humoral immune responses if compared to local (intracerebral) one. The cellular allocytotoxic responses reached their maximum on the 6–12th day after immunization and thereafter gradually decreased to the 37th day . Sandimmun decreased these manifestations in mice with intraperitoneal introduction of the cells starting from the 12th day and did not affect significantly this index in animals with intracerebral introduction. Humoral allocytotoxic responses in mice with intraperitoneal introduction of fetal NPCs achieved their maximum on the 12–18th day and thereafter decreased starting from the 18th till the 37th day. The level of allocytotoxic antibodies decreased down to the norm under the effect of Sandimmun to the 37th day. In mice with intracerebral introduction of the cells the level of humoral allocytotoxic immune responses decreased starting from the 18th day, and was not significantly changed under the effect of Sandimmun. Increased levels of antibodies against MBP (18th day) and S-100 (37th day) were found in mice with intraperitoneal introduction of the fetal NPCs. The mice with intracerebral introduction of foetal NPCs were characterized with more significant immune response to marker antigens of nervous system (MBP and NSE), increased to the 37th day. Sandimmun administration reduced the neural antibodies level down to the norm to the 37th day.