No evidence for circulating HuD-specific CD8+ T cells in patients with paraneoplastic neurological syndromes and Hu antibodies

Abstract

Aim: In paraneoplastic neurological syndromes (PNS) associated with small cell lung cancer (SCLC) and Hu antibodies (Hu-PNS), Hu antigens expressed by the tumour hypothetically trigger an immune response that also reacts with Hu antigens in the nervous system, resulting in tumour suppression and neuronal damage. To gain more insight into the hypothesized CD8+ T cell-mediated immune pathogenesis of these syndromes, we searched for circulating HuD-specific CD8+ T cells in a large cohort of Hu-PNS patients and controls. Patients and methods: Blood was tested from 43 Hu-PNS patients, 31 Hu antibody negative SCLC patients without PNS and 54 healthy controls. Peripheral blood mononuclear cells (PBMC) were stimulated with HuD protein-spanning peptide pools (15-mers) and individual HuD-derived peptides (9-mers) and analysed by cytokine flow cytometry and interferon-γ ELISPOT-assays. Additionally, HuD-based Class I HLA multimers were used to visualize HuD-specific CD8+ T cells. Results: No HuD-specific CD8+ T cells could be detected in the blood of Hu-PNS patients or controls. Conclusions: Our results do not support a role for HuD-specific CD8+ T cells in Hu-PNS. Further studies should focus on the detection of circulating HuD-specific CD4+ T cells and examine the antigen specificity of T cells in affected tissues. © 2007 Springer-Verlag.