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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: |
Tamura, Y., Yamane, K., Kawano, Y., Bullinger, L.  ORCID: https://orcid.org/0000-0002-5890-5510, Wirtz, T. ORCID: https://orcid.org/0009-0005-5677-9804, Weber, T. ORCID: https://orcid.org/0000-0003-2079-842X, Sander, S. ORCID: https://orcid.org/0000-0003-4645-3366, Ohki, S., Kitajima, Y. ORCID: https://orcid.org/0000-0001-6277-5918, Okada, S. ORCID: https://orcid.org/0000-0002-4622-5657, Rajewsky, K. ORCID: https://orcid.org/0000-0002-6633-6370 and Yasuda, T. ORCID: https://orcid.org/0000-0001-9997-6852
|
| 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 |
| Source: | Cancers |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Volume: | 14 |
| Number: | 17 |
| Page Range: | 4118 |
| Date: | 25 August 2022 |
| Official Publication: | https://doi.org/10.3390/cancers14174118 |
| PubMed: | View item in PubMed |
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