2025-12-04 ワシントン大学セントルイス校
<関連情報>
- https://source.washu.edu/2025/12/t-cells-found-in-tonsils-differ-in-key-ways-from-those-in-blood/
- https://www.cell.com/immunity/fulltext/S1074-7613(25)00479-0
ヒトT細胞の詳細なプロファイリングにより、血液と扁桃腺にわたる区画化されたクローンと表現型の軌跡が定義される Deep profiling of human T cells defines compartmentalized clones and phenotypic trajectories across blood and tonsils
Suhas Sureshchandra ∙ James Henderson ∙ Elizabeth Levendosky ∙ … ∙ Andreas Tiffeau-Mayer ∙ Naresha Saligrama ∙ Lisa E. Wagar
Immunity Published:November 26, 2025
DOI:https://doi.org/10.1016/j.immuni.2025.10.025
Graphical abstract
Highlights
- 5.7 million blood and tonsil T cells were profiled using single-cell RNA-seq
- Circulating T cells exhibit limited clonal overlap with their tonsillar counterparts
- Clonal prevalence and dominance of antigen-specific CD8 T cells varied by compartment
- Viral exposure is more influential on tonsillar repertoire diversity than blood
Summary
98% of T cells reside in tissues, yet nearly all human T cell analyses are performed on peripheral blood. We performed single-cell sequencing of 5.7 million T cells from autologous blood and tonsils of ten donors. We identified distinct patterns of clonal expansion associated with tonsil-restricted phenotypes. Clonal sharing between blood and tonsils was lower than previous estimates and increased with age. Identical T cell receptor (TCR) sequences exhibited limited concordance in their phenotypes across compartments. Furthermore, location dictated the frequencies, clonal dominance, and phenotypes of antigen-specific T cells. Using immune organoids, we showed that antigen exposure drives functionally distinct T cell clones from naive or tissue-resident memory pools. Finally, we demonstrate that chronic infections influence TCR repertoire diversity differently in blood and tonsil-resident T cells. These data highlight the necessity of accounting for tissue-specific contexts to accurately measure the TCR repertoire and monitor T cell responses following perturbing therapies.
