Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection

Latent viral infections rely on a precise coordination of the immune response to control sporadic viral reactivation. CD8+ T cells play a crucial role in controlling viral latency by generating diverse memory responses in an epitope-specific manner. Among these distinct responses, conventional and inflationary memory responses have been described during herpesvirus infections. Using a newly generated TCR transgenic mouse strain, we investigated the transcriptomic and epigenetic remodeling of distinct epitope-specific CD8+ T cells during CMV infection across tissues at both population and single-cell levels. Our findings reveal that whereas the transcriptomic and epigenetic landscapes of conventional and inflationary memory responses diverge in the spleen and liver, these molecular programs converge in the salivary gland, a site of CMV persistence. Thus, we provide evidence that the dynamics of memory CD8+ T cell responses are distinct between tissues.

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Publication Details

Journal
The Journal of Experimental Medicine
Published
2025-05-19
DOI
https://doi.org/10.1084/jem.20242078
Citations
3
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
2.39

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article

Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection

Meril Takizawa, Orr-El Weizman, Annette Oxenius, Simon A. Grassmann et al.
3 citations
The Journal of Experimental Medicine
T-cell and B-cell Immunology
2.39
article

Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection

Meril Takizawa, Orr-El Weizman, Annette Oxenius, Simon A. Grassmann, Georg Gasteiger, Endi K. Santosa, Nicholas M. Adams, Brandon D. Ng, J Zhang, Joseph Chai-Yuen Sun, Mariah Lee, Sigrun V. Stulz, Ronan Chaligné, Colleen M. Lau, J. J. Sauter
article en
3 citations

Abstract

Latent viral infections rely on a precise coordination of the immune response to control sporadic viral reactivation. CD8+ T cells play a crucial role in controlling viral latency by generating diverse memory responses in an epitope-specific manner. Among these distinct responses, conventional and inflationary memory responses have been described during herpesvirus infections. Using a newly generated TCR transgenic mouse strain, we investigated the transcriptomic and epigenetic remodeling of distinct epitope-specific CD8+ T cells during CMV infection across tissues at both population and single-cell levels. Our findings reveal that whereas the transcriptomic and epigenetic landscapes of conventional and inflationary memory responses diverge in the spleen and liver, these molecular programs converge in the salivary gland, a site of CMV persistence. Thus, we provide evidence that the dynamics of memory CD8+ T cell responses are distinct between tissues.

The Journal of Experimental MedicineVol. 222(8)
Memorial Sloan Kettering Cancer Center (US), Cornell University (US), University of Würzburg (DE), ETH Zurich (CH), Czech Academy of Sciences, Institute of Microbiology (CZ), New York State College of Veterinary Medicine (US), New York University (US)
American Cancer Society, Burroughs Wellcome Fund, National Institutes of Health, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 11%
T-cell and B-cell Immunology
2.39
DOISourceOpenAlex
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