Biology subjects

Prieux, M.

Publications and source records attributed to Prieux, M..

4 recordsLinked to original sources

bioRxiv2025

A temporary challenge by tumor cells can lead to a permanent partial-impairment of memory CD8 T cell function

Memory CD8 T cells typically exhibit improved effector functions compared to their naive counterparts. However, under certain activation conditions, such as chronic viral infections or cancer, these cells may develop functional defects. In this study, we compared the functional quality of memory CD8 T cells generated following tumor rejection with those arising from an acute viral infection. We found that tumor-induced (Tum-CD8) memory cells exhibited a distinct phenotype and transcriptomic profile compared with viral-induced (Vir-CD8) memory cells. These memory cells are characterized by the expression of inhibitory receptors and displayed altered functions including reduced IFN{gamma} and TNF production as well as changes in integrin expression. Additionally, the protective capacity of Tum-CD8 memory cells was flawed relative to that of Vir-CD8 memory cells. Importantly, the functional defects of Tum-CD8 persisted upon viral recall. Together, these findings indicate that transient tumoral stimulation can imprint a stable partial exhaustion-like program on memory CD8 T cells.

immunology↗

bioRxiv2024

Memory-Phenotype Ly49+ CD8 T emerging from the thymus develop into two subsets with distinct immune functions

Ly49+ CD8 T cells are memory-phenotype (MP) cells expressing Ly49 family inhibitory receptors, that control autoimmune diseases development through the regulation of follicular CD4 T cells. During viral infection, their number increases, suggesting an involvement in antiviral responses. These cells do not derive from naive cells and are thought to develop in the thymus. This study identified two subsets of Ly49+ CD8 T cells, based on CD8{beta} expression, in mice and humans. Lineage tracing and reliance on the transcription factor Zeb1 indicate a thymic origin via agonist selection. scRNAseq analysis revealed that a small fraction of CD8{beta}-Ly49+ cells acquired an effector profile during vaccinia virus infection. Moreover, the majority of Ly49+ CD8 T cells seems to respond to cytokine-driven bystander signals. In vitro, these signals promoted the expression of effector molecules such as IFN{gamma} and granzyme B, as well as the homing chemokine receptor CXCR5, potentially driving their recruitment to germinal centers. SummaryThis study shows that Ly49+ CD8 T cells comprises two subsets that develop in the thymus through agonist selection. In viral infection, both subsets respond to bystander stimuli that could drive their regulatory activity. Furthermore, some CD8{beta}-expressing Ly49+ cells exert TCR-mediated antiviral response.

immunology↗

bioRxiv2022

CD8 memory precursor cells generation is a continuous process

In this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that memory precursors are generated continuously with increasing numbers being generated over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence to differentiate into memory cells was confirmed by BrdU pulse-chase experiment in vivo. Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.

immunology↗

bioRxiv2019

A pivotal genetic program controlled by thyroid hormone during the maturation of GABAergic neurons in mice

In mammals, brain development is critically dependent on proper thyroid hormone signaling, via the TR1 nuclear receptor. However, the downstream mechanisms by which TR1 impacts brain development are currently unknown, notably because this receptor is expressed ubiquitously from early stages of development. In order to better define the function of TR1 in the developing brain, we used mouse genetics to induce the expression of a dominant-negative mutation of the receptor specifically in GABAergic neurons, the main inhibitory neurons in the brain, which were previously identified as sensitive to hypothyroidism. This triggered post-natal epileptic seizures, reflecting a profound impairment of GABAergic neuron maturation in different brain areas. Analysis of transcriptome and TR1 cistrome also allowed us to identify a small set of genes, the transcription of which is upregulated by TR1 in GABAergic neurons during post-natal maturation of the striatum and which probably play an important role during neurodevelopment. Thus, our results point to GABAergic neurons as direct targets of thyroid hormone during brain development and suggest that many defects seen in hypothyroid brains may be secondary to GABAergic neuron malfunction.

developmental biology↗