Universität zu Köln

Tamura, Yumi, Yamane, Keita, Kawano, Yohei, Bullinger, Lars, Wirtz, Tristan, Weber, Timm, Sander, Sandrine ORCID: 0000-0003-4645-3366, Ohki, Shun, Kitajima, Yasuo ORCID: 0000-0001-6277-5918, Okada, Satoshi ORCID: 0000-0002-4622-5657, Rajewsky, Klaus and Yasuda, Tomoharu (2022). Concomitant Cytotoxic Effector Differentiation of CD4(+) and CD8(+) T Cells in Response to EBV-Infected B Cells. Cancers, 14 (17). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary The Epstein-Barr virus (EBV) is a gamma-herpes virus that primarily infects human B cells, and more than 90% of adults have experienced infection. EBV+ B cells express several viral proteins, transmitting signals important for the transformation and tumorigenesis of the infected B cells. Immune surveillance by the host immune system is important to suppress such abnormal expansion of EBV-infected B cells. Here we found that both CD4(+) T cells and CD8(+) T cells show similar gene expression patterns relating to cytotoxicity towards EBV-infected B cells. EBV-specific cytotoxic CD4(+) T cells markedly expressed T-bet, Granzyme B, and Perforin alongside killing activity, which could reflect mechanisms shared with cytotoxic CD8(+) T cells. Our findings support the concept that, upon EBV and perhaps other viral infections, T cells of different subsets can be drawn into common pathways mediating immune surveillance through cytotoxicity. 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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tamura, Yumi UNSPECIFIED UNSPECIFIED UNSPECIFIED Yamane, Keita UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawano, Yohei UNSPECIFIED UNSPECIFIED UNSPECIFIED Bullinger, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Tristan UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Timm UNSPECIFIED UNSPECIFIED UNSPECIFIED Sander, Sandrine UNSPECIFIED orcid.org/0000-0003-4645-3366 UNSPECIFIED Ohki, Shun UNSPECIFIED UNSPECIFIED UNSPECIFIED Kitajima, Yasuo UNSPECIFIED orcid.org/0000-0001-6277-5918 UNSPECIFIED Okada, Satoshi UNSPECIFIED orcid.org/0000-0002-4622-5657 UNSPECIFIED Rajewsky, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Yasuda, Tomoharu UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-690778
DOI:	10.3390/cancers14174118
Journal or Publication Title:	Cancers
Volume:	14
Number:	17
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPSTEIN-BARR-VIRUS; VIRAL-INFECTION; CLONES; LMP1 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69077