Defining molecular circuits of CD8(+) T cell responses in tissues during latent viral infection Journal Article


Authors: Santosa, E. K.; Zhang, J. M.; Sauter, J. C.; Lee, M. E.; Ng, B. D.; Stulz, S. V.; Takizawa, M.; Grassmann, S.; Weizman, O. E.; Adams, N. M.; Chaligné, R.; Oxenius, A.; Gasteiger, G.; Lau, C. M.; Sun, J. C.
Article Title: Defining molecular circuits of CD8(+) T cell responses in tissues during latent viral infection
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. © 2025 Santosa et al.
Keywords: genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; animals; mice; spleen; mice, inbred c57bl; transgenic mouse; c57bl mouse; virology; mice, transgenic; liver; immunology; receptors, antigen, t-cell; epigenesis, genetic; salivary gland; salivary glands; virus latency; genetic epigenesis; transcriptome; cytomegalovirus infection; lymphocyte antigen receptor; immunologic memory; immunological memory; cytomegalovirus infections; muromegalovirus; latent infection
Journal Title: Journal of Experimental Medicine
Volume: 222
Issue: 8
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2025-08-04
Start Page: e20242078
Language: English
DOI: 10.1084/jem.20242078
PUBMED: 40387857
PROVIDER: scopus
PMCID: PMC12087470
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Joseph Sun -- Source: Scopus
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MSK Authors
  1. Joseph C Sun
    130 Sun
  2. Brandon David Ng
    6 Ng
  3. Orrel   Weizman
    11 Weizman
  4. Nicholas M Adams
    19 Adams
  5. Endi Santosa
    13 Santosa
  6. Mariah E Lee
    2 Lee
  7. John Sauter
    2 Sauter
  8. Jennifer Zhang
    1 Zhang