Cellular architecture shapes the naive T cell response

• 成果类型: Article
• 署名作者: Hale, Benjamin D.; Severin, Yannik; Graebnitz, Fabienne; Stark, Dominique; Guignard, Daniel; Mena, Julien; Festl, Yasmin; Lee, Sohyon; Hanimann, Jacob; Zangger, Nathan S.; Meier, Michelle; Goslings, David; Lamprecht, Olga; Frey, Beat M.; Oxenius, Annette; Snijder, Berend
• 署名单位: Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich; Swiss Institute of Bioinformatics
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13068
• DOI: 10.1126/science.adh8967
• 发表日期: 2024-06-07
• 关键词: lymphocytic choriomeningitis virus; memory; effector; maturation; plasticity; lineage; image; fate; mice

摘要

After antigen stimulation, naive T cells display reproducible population-level responses, which arise from individual T cells pursuing specific differentiation trajectories. However, cell-intrinsic predeterminants controlling these single-cell decisions remain enigmatic. We found that the subcellular architectures of naive CD8 T cells, defined by the presence (T-& Oslash;) or absence (T-O) of nuclear envelope invaginations, changed with maturation, activation, and differentiation. Upon T cell receptor (TCR) stimulation, naive T-& Oslash; cells displayed increased expression of the early-response gene Nr4a1, dependent upon heightened calcium entry. Subsequently, in vitro differentiation revealed that T-& Oslash; cells generated effector-like cells more so compared with T-O cells, which proliferated less and preferentially adopted a memory-precursor phenotype. These data suggest that cellular architecture may be a predeterminant of naive CD8 T cell fate.