Journal Article

Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells

McGonagil, Patrick W., Jensen, Isaac J., Bishop, Gail A., Ybarra, Tiffany K., Harty, John T., Berton, Roger R., Griffith, Thomas S., Badovinac, Vladimir P.

2023

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Animals / Biological response modifiers / Biology and life sciences / CD8 antigen / CD8-Positive T-Lymphocytes / Cecum / Cells / Chronic infection / Composition / Cytokine Release Syndrome / Cytokine storm / Cytokines / Disease susceptibility / Disseminated infection / Effector cells / Genetic aspects / Health aspects / Heterogeneity / Humans / Immune response / Immune system / Immunity, Innate / Immunologic Memory / Immunological memory / Infection / Infections / Interferon / Lymphocytes / Lymphocytes T / Medicine and health sciences / Memory cells / Mice / Mice, Inbred C57BL / Pathogens / Peripheral blood / Phenotype / Phenotypes / Representations / Research and Analysis Methods / Sepsis / T cells / Viral infections / Virus diseases