Sepsis is characterized by a disseminated infection, resulting in a hyperinflammatory state, followed by prolonged immunoparalysis which is characterized by severe transient lymphopenia and long-lasting immunological dysregulation.

Our lab focus on naïve and memory CD8 T cell responses after acute infections and/or vaccinations. Upon cognate antigen-encounter naïve Ag-specific CD8 T cells undergo proliferative expansion in numbers and differentiate into effector cells that contribute to pathogen clearance. Thus, the status of naïve CD8 T cell compartment can determine the ability of the host to respond to newly encountered infections.

Sepsis induces rapid and vigorous apoptosis of naïve (Ag-non experienced CD11alow/CD8#913;high CD8 or CD11alow/CD49dlow CD4 T cells) T cells creating a lymphopenic environment supporting homeostatic proliferation (HP) of T cells that survive early ‘cytokine storm’ phase of sepsis. As a consequence of HP and in response to microbes that evoke sepsis, numerical recovery of T cell compartment is accompanied by phenotypic/functional changes (memory-like T cells) on a sizeable fraction of T cells. Sepsis can induce ‘holes’ in the T cell repertoire further contributing to overall changes in the composition of T cell pools, making their subsequent T cell responses to newly encountered pathogens potentially impaired.

One of my projects will be to further delineate sepsis-induced long-lasting functional, epigenetic, and transcriptomic changes in naïve CD8 T cells using state-of-the-art techniques and models readily available in the lab.

Publications

Kannan SK, Kim CY, Heidarian M, Berton RR, Jensen IJ, Griffith TS, Badovinac VP. Mouse Models of Sepsis. Curr Protoc. 2024 Mar;4(3):e997. doi: 10.1002/cpz1.997. Erratum in: Curr Protoc. 2024 Jul;4(7):e1111. doi: 10.1002/cpz1.1111. PMID: 38439603; PMCID: PMC10917121.

Silva EE, Moioffer SJ, Hassert M, Berton RR, Smith MG, van de Wall S, Meyerholz DK, Griffith TS, Harty JT, Badovinac VP. Defining Parameters That Modulate Susceptibility and Protection to Respiratory Murine Coronavirus MHV1 Infection. J Immunol. 2024 Feb 15;212(4):563-575. doi: 10.4049/jimmunol.2300434. PMID: 38149923; PMCID: PMC10872354.

Berton RR, McGonagil PW, Jensen IJ, Ybarra TK, Bishop GA, Harty JT, Griffith TS, Badovinac VP. Sepsis leads to lasting changes in phenotype and function of naïve CD8 T cells. PLoS Pathog. 2023 Oct 12;19(10):e1011720. doi: 10.1371/journal.ppat.1011720. PMID: 37824591; PMCID: PMC10597476.

Moioffer SJ, Berton RR, McGonagill PW, Jensen IJ, Griffith TS, Badovinac VP. Inefficient Recovery of Repeatedly Stimulated Memory CD8 T Cells after Polymicrobial Sepsis Induction Leads to Changes in Memory CD8 T Cell Pool Composition. J Immunol. 2023 Jan 15;210(2):168-179. doi: 10.4049/jimmunol.2200676. PMID: 36480268; PMCID: PMC9840817.

Berton RR, Jensen IJ, Harty JT, Griffith TS, Badovinac VP. Inflammation Controls Susceptibility of Immune-Experienced Mice to Sepsis. Immunohorizons. 2022 Jul 25;6(7):528-542. doi: 10.4049/immunohorizons.2200050. PMID: 35878936; PMCID: PMC9650784.

Jensen IJ, McGonagill PW, Berton RR, Wagner BA, Silva EE, Buettner GR, Griffith TS, Badovinac VP. Prolonged Reactive Oxygen Species Production following Septic Insult. Immunohorizons. 2021 Jun 18;5(6):477-488. doi: 10.4049/immunohorizons.2100027. PMID: 34145054; PMCID: PMC8686528.

Sjaastad FV, Jensen IJ, Berton RR, Badovinac VP, Griffith TS. Inducing Experimental Polymicrobial Sepsis by Cecal Ligation and Puncture. Curr Protoc Immunol. 2020 Dec;131(1):e110. doi: 10.1002/cpim.110. PMID: 33027848; PMCID: PMC7747468.

Danahy DB, Berton RR, Badovinac VP. Cutting Edge: Antitumor Immunity by Pathogen-Specific CD8 T Cells in the Absence of Cognate Antigen Recognition. J Immunol. 2020 Mar 15;204(6):1431-1435. doi: 10.4049/jimmunol.1901172. Epub 2020 Feb 12. PMID: 32051220; PMCID: PMC7310247.

Honors & Awards

• Wallace fellowship - 2021