التفاصيل البيبلوغرافية
| العنوان: |
The gene regulatory basis of bystander activation in CD8+ T cells. |
| المؤلفون: |
Watson, Neva B., Patel, Ravi K., Kean, Connor, Veazey, Janelle, Oyesola, Oyebola O., Laniewski, Nathan, Grenier, Jennifer K., Wang, Jocelyn, Tabilas, Cybelle, Yee Mon, Kristel J., McNairn, Adrian J., Peng, Seth A., Wesnak, Samantha P., Nzingha, Kito, Davenport, Miles P., Tait Wojno, Elia D., Scheible, Kristin M., Smith, Norah L., Grimson, Andrew, Rudd, Brian D. |
| المصدر: |
Science Immunology; 2024, Vol. 9 Issue 92, p1-17, 17p |
| مصطلحات موضوعية: |
T cells, REGULATOR genes, AP-1 transcription factor, T cell receptors, IMMUNE recognition |
| مستخلص: |
CD8+ T cells are classically recognized as adaptive lymphocytes based on their ability to recognize specific foreign antigens and mount memory responses. However, recent studies indicate that some antigen-inexperienced CD8+ T cells can respond to innate cytokines alone in the absence of cognate T cell receptor stimulation, a phenomenon referred to as bystander activation. Here, we demonstrate that neonatal CD8+ T cells undergo a robust and diverse program of bystander activation, which corresponds to enhanced innate-like protection against unrelated pathogens. Using a multi-omics approach, we found that the ability of neonatal CD8+ T cells to respond to innate cytokines derives from their capacity to undergo rapid chromatin remodeling, resulting in the usage of a distinct set of enhancers and transcription factors typically found in innate-like T cells. We observed that the switch between innate and adaptive functions in the CD8+ T cell compartment is mediated by changes in the abundance of distinct subsets of cells. The innate CD8+ T cell subset that predominates in early life was also present in adult mice and humans. Our findings provide support for the layered immune hypothesis and indicate that the CD8+ T cell compartment is more functionally diverse than previously thought. Editor's summary: Although T cells are primarily activated in response to antigen recognition via their T cell receptor (TCR), they can also undergo TCR-independent "bystander" activation in response to certain cytokines. Using single-cell transcriptomics and chromatin accessibility profiling, Watson et al. found that neonatal CD8+ T cells undergo a distinct and robust program of innate-like bystander activation controlled by a balance of Bach2 and AP-1 transcription factor activity. Neonatal CD8+ T cells could protect against bacterial, viral, and parasitic pathogens in a TCR-independent manner. Innate-like CD8+ T cells were also present in both adult mice and humans, indicating that multiple layers of defense may exist within the adult naïve T cell pool. —Claire Olingy [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
