title: Early Effector CD8 T Cells Display Plasticity in Populating the Short-Lived Effector and Memory-Precursor Pools Following Bacterial or Viral Infection.
abstract: Naïve antigen-specific CD8 T cells expand in response to infection and can be phenotypically separated into distinct effector populations, which include memory precursor effector cells (MPECs) and short-lived effector cells (SLECs). In the days before the peak of the T cell response, a third population called early effector cells (EECs) predominate the antigen-specific response. However, the contribution of the EEC population to the CD8 T cell differentiation program during an antimicrobial immune response is not well understood. To test if EEC populations were pre-committed to either an MPEC or SLEC fate, we purified EECs from mice infected with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV), where the relative frequency of each population is known to be different at the peak of the response. Sorted EECs transferred into uninfected hosts revealed that EECs were pre-programmed to differentiate based on early signals received from the distinct infectious environments. Surprisingly, when these same EECs were transferred early into mismatched infected hosts, the transferred EECs could be diverted from their original fate. These results delineate a model of differentiation where EECs are programmed to form MPECs or SLECs, but remain susceptible to additional inflammatory stimuli that can alter their fate.
authors.affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Plumlee
authors.affiliation: Dept. of Immunology &Infectious Disease, Montana State University, Bozeman, MT.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Obar
authors.affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Colpitts
authors.affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Jellison
authors.affiliation: Dept. of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: W Nicholas
authors.initials: WN
authors.lastname: Haining
authors.affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrancois
authors.affiliation: 1] Dept. of Immunology, University of Connecticut Health Center, Farmington, CT [2] Dept of Pediatrics, University of Connecticut Health Center, Farmington, CT.
authors.forename: Kamal M
authors.initials: KM
authors.lastname: Khanna
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D016678:Genome; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D018116:Vesiculovirus / Q000502:physiology; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D000941:Antigens