Immunosuppression with monoclonal antibodies in neural transplantation

Thesis

The ability of two different immunosuppressive monoclonal antibodies to prolong the survival and function of neural allografts and xenografts in mice and rats was studied.

YTS 191.1, a rat IgG2b monoclonal antibody against the L3T4 surface antigen found on murine helper T-cells, was injected intraperitoneally into mice for thirteen consecutive days. Mice received various grafts of central nervous system (CNS) tissue to their third ventricle or parenchyma on the third day. The mice were examined to observe the specific depletion of helper T-cells and the neural grafts were examined histologically for surviving tissue at various time points. Mice immunosuppressed with YTS 191.1 had significant prolongation of both allograft and xenograft tissue compared to control animals given saline or an antibody against the Lyt-2 surface antigen on cytotoxic T-cells. Xenografts of rat neuronal tissue containing gonadotrophin releasing hormone neurons were shown to function in the third ventricle of hypogonadal mice at thirty days.

NDS 63, a mouse IgG1 monoclonal antibody against the rat interleukin-2 receptor, found on activated T-cells, was injected intraperitoneally into rats for ten consecutive days. The rats received CNS allografts and xenografts to their third ventricle and striatum on day one. Rats irnmunosuppressed with NDS 63 had significant prolongation of survival of all neural grafts. Fetal human mesencephalon was shown to function for at least six months in a hemi-Parkinson model of rats irnmunosuppressed with NDS 63.

The benefits of monoclonal antibodies for immunosuppression was discussed.

Authors: Honey, C

• Publication date: 1990
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Immunosuppression; Central nervous system; Transplantation; Monoclonal antibodies; Nerve tissue