title: No evidence for circulating HuD-specific CD8+ T cells in patients with paraneoplastic neurological syndromes and Hu antibodies.
abstract: OBJECTIVE
  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.
  
  
  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-gamma 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.
authors.affiliation: Department of Medical Oncology, Room E-2-80B, Erasmus University Medical Center, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
authors.forename: Janet W
authors.initials: JW
authors.lastname: de Beukelaar
authors.forename: Georges M
authors.initials: GM
authors.lastname: Verjans
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Norden
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Milikan
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.forename: Herbert
authors.initials: H
authors.lastname: Hooijkaas
authors.forename: Kees
authors.initials: K
authors.lastname: Sintnicolaas
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D051959:ELAV Proteins / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D000906:Antibodies; D051959:ELAV Proteins