title: Polymicrobial sepsis alters antigen-dependent and -independent memory CD8 T cell functions.
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.
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, IA 52242;
authors.forename: Sean
authors.initials: S
authors.lastname: Duong
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Condotta
authors.forename: Deepa
authors.initials: D
authors.lastname: Rai
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Martin
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Badovinac
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D007113:Immunity, Innate; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D000941:Antigens; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma