Hale et al. investigated the morphological heterogeneity of primary human and murine T cells and demonstrated that cellular architecture can determine the fate of naive CD8+ T cells. The subcellular architectures of naive T cells were defined by the presence (TØ) or absence (TO) of nuclear envelope invaginations, which spatially concentrated cellular machinery, including the endoplasmic reticulum, mitochondria, and nuclear pore complexes. In response to TCR stimulation, TØ cells engaged in stronger TCR signaling and differentiated into effector-like cells, whereas TO cells showed dampened TCR signaling and preferentially adopted a memory precursor phenotype.
Contributed by Shishir Pant
ABSTRACT: After antigen stimulation, naïve 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 naïve CD8 T cells, defined by the presence (TØ) or absence (TO) of nuclear envelope invaginations, changed with maturation, activation, and differentiation. Upon T cell receptor (TCR) stimulation, naïve TØ cells displayed increased expression of the early-response gene Nr4a1, dependent upon heightened calcium entry. Subsequently, in vitro differentiation revealed that TØ cells generated effector-like cells more so compared with TO cells, which proliferated less and preferentially adopted a memory-precursor phenotype. These data suggest that cellular architecture may be a predeterminant of naïve CD8 T cell fate.
Author Info: (1) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (2) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Z
Author Info: (1) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (2) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (3) Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland. (4) Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland. (5) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (6) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (7) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (8) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (9) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (10) Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland. (11) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürich, Switzerland. (12) Blood Transfusion Service Zürich, Swiss Red Cross (SRC), Schlieren, Switzerland. (13) Blood Transfusion Service Zürich, Swiss Red Cross (SRC), Schlieren, Switzerland. (14) Blood Transfusion Service Zürich, Swiss Red Cross (SRC), Schlieren, Switzerland. (15) Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, Switzerland. (16) Institute of Molecular Systems Biology, Department of Biology, ETH Zürich, Zürichh, Switzerland. Swiss Institute of Bioinformatics, Lausanne, Switzerland. Comprehensive Cancer Center Zurich (CCCZ), Zürich, Switzerland.
