Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions

Sean Duong; Stephanie A Condotta; Deepa Rai; Matthew D Martin; Thomas S Griffith; Vladimir P Badovinac

doi:10.4049/jimmunol.1303460

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Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions

Journal article

Peer reviewed

Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions

Sean Duong, Stephanie A Condotta, Deepa Rai, Matthew D Martin, Thomas S Griffith and Vladimir P Badovinac

The Journal of immunology (1950), Vol.192(8), pp.3618-3625

04/15/2014

DOI: 10.4049/jimmunol.1303460

PMCID: PMC4001259

PMID: 24646738

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Abstract

Mortality from sepsis frequently results from secondary infections, and the extent to which sepsis affects pathogen-specific memory CD8 T cell responses remains unknown. Using the cecal ligation and puncture model of polymicrobial sepsis, we observed rapid apoptosis of pre-existing memory CD8 T cells after sepsis induction that led to a loss in CD8 T cell-mediated protection. Ag sensitivity (functional avidity) and Ag-driven secondary expansion of memory CD8 T cells were decreased after sepsis, further contributing to the observed loss in CD8 T cell-mediated immunity. Moreover, Ag-independent bystander activation of memory CD8 T cells in response to heterologous infection was also significantly impaired early after sepsis induction. The reduced sensitivity of pre-existing memory CD8 T cells to sense inflammation and respond to heterologous infection by IFN-γ production was observed in inbred and outbred hosts and controlled by extrinsic (but not cell-intrinsic) factors, suggesting that sepsis-induced changes in the environment regulate innate functions of memory CD8 T cells. Taken together, the data in this study revealed a previously unappreciated role of sepsis in shaping the quantity and functionality of infection- or vaccine-induced memory CD8 T cells and will help further define the decline in T cell-mediated immunity during the sepsis-induced phase of immunosuppression.

Sepsis - immunology

Receptors, Antigen, T-Cell - metabolism

Immunity, Innate

Sepsis - virology

Immunosuppression

Lymphocyte Activation - immunology

Animals

CD8-Positive T-Lymphocytes - metabolism

Lymphocyte Count

Antigens - immunology

Immunologic Memory

Mice

Sepsis - blood

CD8-Positive T-Lymphocytes - immunology

Interferon-gamma - biosynthesis

Sepsis - microbiology

Disease Models, Animal

Details

Title: Subtitle: Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions
Creators: Sean Duong - Department of Pathology, University of Iowa, Iowa City, IA 52242
Stephanie A Condotta
Deepa Rai
Matthew D Martin
Thomas S Griffith
Vladimir P Badovinac
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.192(8), pp.3618-3625
DOI: 10.4049/jimmunol.1303460
PMID: 24646738
PMCID: PMC4001259
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: I01 BX001324 / BLRD VA AI83286 / NIAID NIH HHS R21 AI096850 / NIAID NIH HHS R01 AI083286 / NIAID NIH HHS
Language: English
Date published: 04/15/2014
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047703402771

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