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dc.contributor.authorElkord, Eyad
dc.contributor.authorWilliams, Paul E
dc.contributor.authorKynaston, Howard
dc.contributor.authorRowbottom, Anthony W
dc.date.accessioned2009-07-21T16:57:03Z
dc.date.available2009-07-21T16:57:03Z
dc.date.issued2005-10
dc.identifier.citationDifferential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer. 2005, 17 (10):1315-25 Int. Immunol.en
dc.identifier.issn0953-8178
dc.identifier.pmid16141246
dc.identifier.doi10.1093/intimm/dxh309
dc.identifier.urihttp://hdl.handle.net/10541/74823
dc.description.abstractInduction 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.
dc.language.isoenen
dc.subjectProstate Canceren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshCD8-Positive T-Lymphocytes
dc.subject.meshCell Line
dc.subject.meshCytotoxicity Tests, Immunologic
dc.subject.meshFemale
dc.subject.meshHLA-A2 Antigen
dc.subject.meshHumans
dc.subject.meshImmunologic Memory
dc.subject.meshInterferon-gamma
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPeptide Fragments
dc.subject.meshProstate-Specific Antigen
dc.subject.meshProstatic Neoplasms
dc.subject.meshProtein Binding
dc.subject.meshT-Lymphocyte Subsets
dc.subject.meshT-Lymphocytes, Cytotoxic
dc.titleDifferential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK. eelkord@picr.man.ac.uken
dc.identifier.journalInternational Immunologyen
html.description.abstractInduction 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.


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