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

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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-g 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.

Original languageEnglish (US)
Pages (from-to)3618-3625
Number of pages8
JournalJournal of Immunology
Volume192
Issue number8
DOIs
StatePublished - Apr 15 2014

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