Vanhoutte, V.J., McAulay, K.A., McCarrell, E., Turner, M., Crawford, D.H. and Haque, T. (2009) Cytolytic mechanisms and T-cell receptor Vβ usage byex vivogenerated Epstein-Barr virus-specific cytotoxic T lymphocytes. Immunology, 127(4), pp. 577-586. (doi: 10.1111/j.1365-2567.2008.03035.x)
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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2567.2008.03035.x
Abstract
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 β-chain of the TCR revealed that TCR repertoire remained diverse during the course of culture. Cytotoxicity of CTL was significantly inhibited by concanamycin A (<i>P</i> < 0•0001) and ethylene glycol-bis tetraacetic acid (<i>P</i> < 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-γ (IFN-γ) or tumour necrosis factor-α (TNF-α) upon restimulation with autologous LCL, although there were some polyfunctional cells producing IFN-γ and TNF-α. Granzyme B, perforin and Fas ligand were detected in CD8+ and CD4<sup>+</sup> cells in all CTL; however, a greater proportion of CD8<sup>+</sup> than CD4<sup>+</sup> T cells expressed granzyme B (<i>P</i> < 0•0001) and more granzyme B was detected in CD8<sup>+</sup> T cells than in CD4<sup>+</sup> T cells (<i>P</i> = 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McAulay, Dr Karen |
| Authors: | Vanhoutte, V.J., McAulay, K.A., McCarrell, E., Turner, M., Crawford, D.H., and Haque, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Immunology |
| ISSN: | 0019-2805 |
| ISSN (Online): | 1365-2567 |
| Published Online: | 24 December 2008 |
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