ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.173489
1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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1Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
2Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Germany
3Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
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Published September 12, 2024 - More info
Epstein Barr virus (EBV) contributes to around 2% of all tumors worldwide. Simultaneously, more than 90% of healthy human adults persistently carry EBV without clinical symptoms. In most EBV carriers it is thought that virus-induced tumorigenesis is prevented by cell-mediated immunity. Specifically, memory CD8+ T cells recognize EBV-infected cells during latent and lytic infection. Using a symptomatic primary infection model, similar to infectious mononucleosis (IM), we found EBV-induced CD8+ tissue-resident memory T cells (TRMs) in mice with a humanized immune system. These human TRMs were preferentially established after intranasal EBV infection in nasal-associated lymphoid tissues (NALT), equivalent to tonsils, the primary site of EBV infection in humans. They expressed canonical TRM markers, including CD69, CD103, and BLIMP-1, as well as Granzyme B, CD107a and CCL5. Despite cytotoxic activity and cytokine production ex vivo, these TRMs demonstrated reduced CD27 expression and proliferation and failed to control EBV viral loads in the NALT during infection although effector memory T cells (TEMs) controlled viral titers in spleen and blood. Overall, TRMs are established in mucosal lymphoid tissues by EBV infection, but primarily systemic CD8+ T cell expansion seems to control viral loads in the context of IM-like infection.