ArticleCell reports2022
Spatial transcriptomics demonstrates the role of CD4 T cells in effector CD8 T cell differentiation during chronic viral infection.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 20 citations in OpenAlex.
- Spatial Transcriptomics to Study Virus-Host Interactions.Annual review of virology · 2025Review
- Elucidating Sex-Specific Immune Profiles in a Breast Cancer Model.International journal of molecular sciences · 2024Article
- STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics.Advances in neural information processing systems · 2024Article
- The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.Immune network · 2023Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
CD4 T cell help is critical to sustain effector CD8 T cell responses during chronic infection, notably via T follicular helper (Tfh)-derived interleukin-21 (IL-21). Conversely, CD4 depletion results in severe CD8 T cell dysfunction and lifelong viremia despite CD4 T cell reemergence following transient depletion. These observations suggest that repopulating CD4 subsets are functionally or numerically insufficient to orchestrate a robust CD8 response. We utilize spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) to investigate CD4 T cell heterogeneity under CD4-replete and -deplete conditions and explore cellular interactions during chronic infection. Although IL-21-producing Tfh cells repopulate following transient CD4 depletion, they are outnumbered by immunomodulatory CD4 T cells. Moreover, the splenic architecture appears perturbed, with decreases in white pulp regions, coinciding with germinal center losses. These disruptions in splenic architecture are associated with diminished Tfh and progenitor CD8 T cell colocalization, providing a potential mechanism for impaired progenitor-to-effector CD8 T cell differentiation during "un-helped" conditions.
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Registered trials
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