Investigation of cytotoxic T lymphocyte responses to the HuD and Yo antigens in individuals with paraneoplastic neurological syndromes

• Main Author: Sutton, Ian
• Published: University of Birmingham 2002
• Subjects: 616; Medicine
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274426

High titres of antibodies reactive with neuronal antigens are found within the serum of individuals with paraneoplastic encephalomyelitis/subacute sensory neuropathy (anti-Hu) and paraneopiastic cerebellar degeneration (anti-Yo). However, neither the anti-Hu nor the anti-Yo antibody response has demonstrable pathogenic effects. The work presented in this thesis examines whether cytotoxic T lymphocyte (CTL) responses to Hu and Yo antigens could mediate neuronal and tumour cell destruction. HuD and Yo genes were cloned into expression cassettes which were then cloned into replication-defective adenoviruses. Peripheral blood CTL responses in patients with paraneoplastic neurological syndromes were examined by using autologous dendritic cells infected with these recombinant adenoviruses as antigen presenting cells in an ex vivo interferon-y Elispot assay. No CD8+ CTL responses specific for epitopes derived from HuD or Yo could be detected in six patients with paraneoplastic syndromes (4 anti-Hu, 2 anti-Yo) and impaired CD8+ CTL responses to adenoviral-derived antigens were observed in this patient group. No HuD specific CTL responses could be detected in polyclonal T cell lines derived from sural nerve biopsies taken from 2 patients with subacute sensory neuropathy and immunohistochemical studies demonstrated that only 2/9 tumour sections from patients with anti-Yo antibodies contained CD8+ tumour infiltrating lymphocytes.