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Cytolytic mechanisms and T-cell receptor Vβ usage byex vivogenerated Epstein-Barr virus-specific cytotoxic T lymphocytes
| Content Provider | Scilit |
|---|---|
| Author | Vanhoutte, Victoria J. McAulay, Karen A. McCarrell, Erin Turner, Marc Crawford, Dorothy H. Haque, Tanzina |
| Copyright Year | 2009 |
| Description | Journal: Immunology Ex-vivo-generated Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) have been used for cellular adoptive immunotherapy of EBV-associated lymphomas. Here we investigated the phenotypes, cytolytic mechanisms, polyfunctionality and T-cell receptor (TCR) usage in growing and established CTL, generated by weekly stimulation with an EBV-transformed autologous lymphoblastoid cell line (LCL). Our results showed that phenotypically mature CTL developed within the first 4 weeks of culture, with an increase in CD45RO and CD69, and a decrease in CD45RA, CD62L, CD27 and CD28 expression. Spectratyping analysis of the variable beta-chain of the TCR revealed that TCR repertoire remained diverse during the course of culture. Cytotoxicity of CTL was significantly inhibited by concanamycin A (P < 0.0001) and ethylene glycol-bis tetraacetic acid (P < 0.0001), indicating that a calcium and perforin-mediated exocytosis pathway with the release of granzyme B was the principal cytotoxic mechanism. The CTL mainly produced interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) upon restimulation with autologous LCL, although there were some polyfunctional cells producing IFN-gamma and TNF-alpha. Granzyme B, perforin and Fas ligand were detected in CD8(+) and CD4(+) cells in all CTL; however, a greater proportion of CD8(+) than CD4(+) T cells expressed granzyme B (P < 0.0001) and more granzyme B was detected in CD8(+) T cells than in CD4(+) T cells (P = 0.001). This difference was not observed with Fas ligand or perforin expression. Our results provide insight into the basic characteristics of ex-vivo-generated CTL. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729535/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2567.2008.03035.x/pdf |
| Ending Page | 586 |
| Page Count | 10 |
| Starting Page | 577 |
| e-ISSN | 13652567 |
| DOI | 10.1111/j.1365-2567.2008.03035.x |
| Journal | Immunology |
| Issue Number | 4 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2009-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Immunology Cytolytic Pathways Cytotoxic T Lymphocytes Epstein–barr Virus T‐cell Receptor |
| Content Type | Text |
| Resource Type | Article |
