Trial of cytotoxic T cell induction in mice as an ex vivo model of paraneoplastic neurologic syndrome with anti-Hu antibodies

Abstract

The pathogenesis of neuronal damage in anti-Hu-antibody-positive paraneoplastic neurologic syndrome (Hu-PNS) is thought to be mediated by cytotoxic T lymphocyte (CTL). However, there is no direct evidence showing that antigen-specific T cells are the effector against neurons. Antigen-specific CTL-mediated cell death has been observed in cancer immunology, but not as a neurological disease model. The CTL-mediated etiology in PNS should be confirmed using in vivo model systems in the future. Herein, we present an ex vivo model of antigen-specific CTL against cultured neurons. A previous study showed the CTL activity of CD8⁺ T cells taken from the peripheral blood of patients with Hu-antibody-positive PNS against Hu-protein-derived-peptide-expressing autologous fibroblasts. Results revealed that the HuD peptide, which can bind to major histocompatibility complex (MHC) class I of Balb/c mice, stimulated CD8⁺ T cells collected from mice immunized with peptide-bound self-activated dendritic cells with murine CD40 ligand-transduced adenovirus vectors (AdmCD40L). Moreover, CTL activity against autologous neurons in culture was observed. Hence, this result could be used in the development of an in vivo model of CTL-induced neurological disorders, which can help in further understanding the pathogenesis of PNS.