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    Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer.

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    Authors
    Elkord, Eyad
    Williams, Paul E
    Kynaston, Howard
    Rowbottom, Anthony W
    Affiliation
    Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK. eelkord@picr.man.ac.uk
    Issue Date
    2005-10
    
    Metadata
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    Abstract
    Induction of CTL responses specific for prostate-specific antigen (PSA)-derived peptides in healthy individuals and patients with prostate cancer (PC) was investigated. Eight PSA-derived peptides that have the potential to bind HLA-A2 molecules were examined. Peripheral blood lymphocytes isolated from HLA-A2-positive volunteers were expanded using autologous mature, PSA-derived peptide-pulsed dendritic cells. The expansion of IFN-gamma-secreting CD8+ T cells specific for three of the eight PSA-derived peptides (PSA-2(108-117), PSA-4(141-150) and PSA-6(146-154)) was detected in healthy individuals, but not in patients with PC. Using HLA-A2/peptide tetramers, the PSA-specific CD8+ T cells were detectable at low frequency both in healthy individuals and patients with PC. Using flow cytometric cytotoxicity assays, the expanded effectors from healthy individuals were able to kill the PSA-expressing epithelial cell line LNCaP and the peptide-pulsed T2 cells in a MHC class I-restricted manner without involving NK activity. However, such killing by effectors expanded from prostatectomized patients involved a complete or a significant NK activity. Specific recognition of PSA-derived peptides in healthy individuals may occur by an adaptive CTL immune response, while such recognition in PC patients may additionally or alternatively be mediated by an innate NK immune response. In conclusion, our work indicates that the PSA-specific CD8+ T cells exist in both healthy individuals and PC patients, but they have impaired function in patients as they failed to release IFN-gamma and to kill targets without involving NK activity.
    Citation
    Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer. 2005, 17 (10):1315-25 Int. Immunol.
    Journal
    International Immunology
    URI
    http://hdl.handle.net/10541/74823
    DOI
    10.1093/intimm/dxh309
    PubMed ID
    16141246
    Type
    Article
    Language
    en
    ISSN
    0953-8178
    ae974a485f413a2113503eed53cd6c53
    10.1093/intimm/dxh309
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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