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Concomitant cytotoxic effector differentiation of CD4+ and CD8+ T Cells in response to EBV-infected B cells

Most people infected by EBV acquire specific immunity, which then controls latent infection throughout their life. Immune surveillance of EBV-infected cells by cytotoxic CD4+ T cells has been recognized; however, the molecular mechanism of generating cytotoxic effector T cells of the CD4+ subset rem...

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Main Authors: Tamura, Yumi (Author) , Yamane, Keita (Author) , Kawano, Yohei (Author) , Bullinger, Lars (Author) , Wirtz, Tristan (Author) , Weber, Timm (Author) , Sander, Sandrine (Author) , Ohki, Shun (Author) , Kitajima, Yasuo (Author) , Okada, Satoshi (Author) , Rajewsky, Klaus (Author) , Yasuda, Tomoharu (Author)
Format: Article (Journal)
Language:English
Published: 25 August 2022
In: Cancers
Year: 2022, Volume: 14, Issue: 17, Pages: 1-16
ISSN:2072-6694
DOI:10.3390/cancers14174118
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14174118
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/17/4118
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Author Notes:Yumi Tamura, Keita Yamane, Yohei Kawano, Lars Bullinger, Tristan Wirtz, Timm Weber, Sandrine Sander, Shun Ohki, Yasuo Kitajima, Satoshi Okada, Klaus Rajewsky and Tomoharu Yasuda
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Summary:Most people infected by EBV acquire specific immunity, which then controls latent infection throughout their life. Immune surveillance of EBV-infected cells by cytotoxic CD4+ T cells has been recognized; however, the molecular mechanism of generating cytotoxic effector T cells of the CD4+ subset remains poorly understood. Here we compared phenotypic features and the transcriptome of EBV-specific effector-memory CD4+ T cells and CD8+ T cells in mice and found that both T cell types show cytotoxicity and, to our surprise, widely similar gene expression patterns relating to cytotoxicity. Similar to cytotoxic CD8+ T cells, EBV-specific cytotoxic CD4+ T cells from human peripheral blood expressed T-bet, Granzyme B, and Perforin and upregulated the degranulation marker, CD107a, immediately after restimulation. Furthermore, T-bet expression in cytotoxic CD4+ T cells was highly correlated with Granzyme B and Perforin expression at the protein level. Thus, differentiation of EBV-specific cytotoxic CD4+ T cells is possibly controlled by mechanisms shared by cytotoxic CD8+ T cells. T-bet-mediated transcriptional regulation may explain the similarity of cytotoxic effector differentiation between CD4+ T cells and CD8+ T cells, implicating that this differentiation pathway may be directed by environmental input rather than T cell subset.
Item Description:Gesehen am 31.10.2022
Physical Description:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14174118

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