Transcriptome analysis and cytokine profiling of naive T cells stimulated by a tumor vaccine via CD3 and CD25

  • Authors:
    • Philippe Fournier
    • Maximilian Aigner
    • Volker Schirrmacher
  • View Affiliations

  • Published online on: December 1, 2010     https://doi.org/10.3892/ijo_00000796
  • Pages: 1439-1452
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Abstract

T-cell receptor engagement by peptide/MHC complexes constitutes the main signal for the activation of naive T cells, but for a productive generation and maintenance of effector cells, full activation requires additional signals driven by costimulatory molecules present on activated antigen-presenting cells. Herein we describe T cell costimulation via CD25, the interleukin (IL)-2 receptor, during priming of naive T cells with a tumor vaccine. To this end, we produced, purified and characterized the fusion protein bsHN-IL2 which contains the IL-2 cytokine and an antibody scFv fragment directed towards the Hemagglutinin-Neuraminidase (HN) protein of Newcastle Disease Virus (NDV). Tumor vaccine cells were modified by infection with this virus which allows the attachment of the immunocytokine bsHN-IL2. In the presence of CD3-mediated signal 1, the vaccine/bsHN-IL2 provided via CD25 a strong bystander antitumor effect in vitro leading to tumor growth inhibition, even stronger than the vaccine/bsHN-CD28 which provides costimulation via CD28. Transcriptome analysis of naive T cells which were stimulated with the vaccine/bsHN-IL2 showed, similarly to the vaccine/bsHN-CD28, upregulation of 71 genes belonging to different signalling pathways, including PLC-γ1, Grb-2, Vav-1 and PDE-4A. Analysis of the supernatants of activated T cells with ligand-bound tumor vaccine showed that the vaccine/bsHN-IL2, in contrast to the vaccine/bsHN-CD28, did not lead to the production of additional IL-2. We report here the first transcriptome analysis of IL-2 receptor mediated costimulatory signals. The findings provide new insights into mechanisms of function of IL-2 during T cell priming.

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December 2010
Volume 37 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Fournier P, Aigner M and Schirrmacher V: Transcriptome analysis and cytokine profiling of naive T cells stimulated by a tumor vaccine via CD3 and CD25. Int J Oncol 37: 1439-1452, 2010
APA
Fournier, P., Aigner, M., & Schirrmacher, V. (2010). Transcriptome analysis and cytokine profiling of naive T cells stimulated by a tumor vaccine via CD3 and CD25. International Journal of Oncology, 37, 1439-1452. https://doi.org/10.3892/ijo_00000796
MLA
Fournier, P., Aigner, M., Schirrmacher, V."Transcriptome analysis and cytokine profiling of naive T cells stimulated by a tumor vaccine via CD3 and CD25". International Journal of Oncology 37.6 (2010): 1439-1452.
Chicago
Fournier, P., Aigner, M., Schirrmacher, V."Transcriptome analysis and cytokine profiling of naive T cells stimulated by a tumor vaccine via CD3 and CD25". International Journal of Oncology 37, no. 6 (2010): 1439-1452. https://doi.org/10.3892/ijo_00000796