Cytotoxic T cell mediated paraneoplastic neurological syndromes

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Paraneoplastic sensory neuronopathy (PSN) has been shown to harbor characteristic antineuronal autoantibody "anti-Hu" in their sera and cerebrospinal fluid. Creation of animal models exhibiting clinical or pathological features seen in PSN by means of passive transfer of anti-Hu positive IgG has not been achieved. Although, anti-Hu antibody was shown to induce neuronal cell lysis in vitro, this result has not been reproduced so far. Since prominent T cell infiltration are seen in the central nervous system and posterior spinal ganglion of the patients with anti-Hu syndrome, we studied cytotoxic T cell (CTL) activety in peripheral mononuclear cells from a pantient with PSN harboring anti-Hu antibody. The activated CD8+ T cells from the pantient's venous blood were shown to lyse her own fibroblasts which were incubated with interferon-alpha to induce HLA class I molecules on their surface and the recombinant HuD protein was injected into the cells by microinjector. This is the first report showning the existence of CTL in a patient with PSN.