Academic Journal
Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells.
العنوان: | Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells. |
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المؤلفون: | Roger R Berton, Patrick W McGonagil, Isaac J Jensen, Tiffany K Ybarra, Gail A Bishop, John T Harty, Thomas S Griffith, Vladimir P Badovinac |
المصدر: | PLoS Pathogens, Vol 19, Iss 10, p e1011720 (2023) |
بيانات النشر: | Public Library of Science (PLoS), 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
الوصف: | Sepsis, an amplified immune response to systemic infection, is characterized by a transient cytokine storm followed by chronic immune dysfunction. Consequently, sepsis survivors are highly susceptible to newly introduced infections, suggesting sepsis can influence the function and composition of the naïve CD8 T cell pool and resulting pathogen-induced primary CD8 T cell responses. Here, we explored the extent to which sepsis induces phenotypic and functional changes within the naïve CD8 T cell pool. To interrogate this, the cecal ligation and puncture (CLP) mouse model of polymicrobial sepsis was used. In normal, non-septic mice, we show type-I interferon (IFN I)-mediated signaling plays an important role in driving the phenotypic and functional heterogeneity in the naïve CD8 T cell compartment leading to increased representation of Ly6C+ naïve CD8 T cells. In response to viral infection after sepsis resolution, naïve Ly6C+ CD8 T cells generated more primary effector and memory CD8 T cells with slower conversion to a central memory CD8 T cell phenotype (Tcm) than Ly6C- naïve CD8 T cells. Importantly, as a potent inducer of cytokine storm and IFN I production, sepsis leads to increased representation of Ly6C+ naïve CD8 T cells that maintained their heightened ability to respond (i.e., effector and memory CD8 T cell accumulation and cytokine production) to primary LCMV infection. Lastly, longitudinal analyses of peripheral blood samples obtained from septic patients revealed profound changes in CD8 T cell subset composition and frequency compared to healthy controls. Thus, sepsis has the capacity to alter the composition of naïve CD8 T cells, directly influencing primary CD8 T cell responses to newly introduced infections. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1553-7366 1553-7374 |
Relation: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011720&type=printable; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
DOI: | 10.1371/journal.ppat.1011720&type=printable |
DOI: | 10.1371/journal.ppat.1011720 |
URL الوصول: | https://doaj.org/article/003cece2a6b74de48c7dbeb1d175f5a5 |
رقم الانضمام: | edsdoj.003cece2a6b74de48c7dbeb1d175f5a5 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 15537366 15537374 |
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DOI: | 10.1371/journal.ppat.1011720&type=printable |