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Concomitant cytotoxic effector differentiation of CD4(+) and CD8(+) T cells in response to EBV-Infected B cells

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Item Type:Article
Title:Concomitant cytotoxic effector differentiation of CD4(+) and CD8(+) T cells in response to EBV-Infected B cells
Creators Name:Tamura, Y. and Yamane, K. and Kawano, Y. and Bullinger, L. and Wirtz, T. and Weber, T. and Sander, S. and Ohki, S. and Kitajima, Y. and Okada, S. and Rajewsky, K. and Yasuda, T.
Abstract: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.
Keywords:Epstein-Barr Virus, LMP1, LMP2A, Lymphoblastoid Cell Line, CD4+ CTL, T-Bet, Eomes, Granzyme B, Perforin, CD107a, Animals, Mice
Page Range:4118
Date:25 August 2022
Official Publication:https://doi.org/10.3390/cancers14174118
PubMed:View item in PubMed

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