The development of anti-PD-1 antibody-induced spinal cord injury in bone marrow transplant C57BL/6 Rag1 mouse model

Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI).Methods: Bone marrow transplant Rag1 mice were used to establish SCI model.Results: Anti-PD-1 results in SCI via CD8⁺ T-cells activation, while excessive activation of CD8⁺ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8⁺ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8⁺ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8⁺ T-cells activation via perforin/GrB/PI-9/FasL pathways.Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.