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International Immunology Advance Access published online on September 1, 2005
International Immunology, doi:10.1093/intimm/dxh309
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Received May 9, 2005
Accepted July 15, 2005

Article

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

Eyad Elkord 1*, Paul E. Williams 2, Howard Kynaston 3, and Anthony W. Rowbottom 4

1 Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK; Present address: CRUK Immunology Department, Paterson Institute for Cancer Research, Manchester M20 4BX, UK
2 Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK; Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, UK
3 Department of Urology, University Hospital of Wales, Cardiff, UK
4 Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, UK

* To whom correspondence should be addressed.
Eyad Elkord, E-mail: eelkord{at}picr.man.ac.uk


  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-2108-117, PSA-4141-150 and PSA-6146-154) 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.

Keywords: cytotoxic T lymphocytes; dendritic cells; NK activity; prostate cancer; prostate-specific antigen.
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