[A study on pathomechanisms of paraneoplastic neurological syndrome]

Paraneoplastic neurological syndrome is thought to be caused by an autoimmune mechanism triggered by tumor antigens which attack the neurons presenting the common antigens. We tried to prove the antibody-mediated neuronal loss by passive transfer with IgG containing Yo antibody or Hu antibody and active immunization with recombinant Yo protein or Hu protein. But in fact the antibody per se did not cause neuronal loss. On the other hand, the patients with paraneoplastic neurological syndrome show pleocytosis in the cerebrospinal fluid and massive lymphorrhage, predominant CD8+ T cells, are seen in the tumor and in the lesions in the central nervous system. Another observation that each of the patients' group with anti-Yo antibody positive paraneoplastic cerebellar degeneration or anti-Hu positive sensory neuronopathy have the common HLA class I supertype, suggested the neuronal loss might be caused by class I restricted CD8-positive cytotoxic T lymphocytes (CTL). We synthesized the peptides from Yo or Hu protein with binding capacity to each of the class I molecules. We found the CTL activities in the peripheral CD8+ T cells against the matched peptide-presenting autologous fibroblasts. We need to prove the CTL attacks neurons directly.