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Early Effector CD8 T Cells Display Plasticity in Populating the Short-Lived Effector and Memory-Precursor Pools Following Bacterial or Viral Infection.

Plumlee CR, Obar JJ, Colpitts SL, Jellison ER, Haining WN, Lefrancois L, Khanna KM - Sci Rep (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.

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.

No MeSH data available.


Related in: MedlinePlus

With time, EECs lose their ability to generate MPEC and SLEC in the absence of exogenous inflammatory stimuli.A. 14 days following VSV-OVA infection, EECs were purified as in Fig. 2A and transferred into day 2 LM-OVA- or VSV-OVA-infected recipients. 6 days following EEC transfer, CD8 CD45.1+ EECs were analyzed for KLRG1 and CD127 expression. Each condition was repeated at least 2 times. B. Day 14 purified EECs from VSV-OVA infection were transferred into uninfected recipients, and CD8 CD45.1+ EECs in the spleen were analyzed for KLRG1 and CD127 expression 3 or 6 days following transfer. Each condition was repeated at least 2 times.
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f6: With time, EECs lose their ability to generate MPEC and SLEC in the absence of exogenous inflammatory stimuli.A. 14 days following VSV-OVA infection, EECs were purified as in Fig. 2A and transferred into day 2 LM-OVA- or VSV-OVA-infected recipients. 6 days following EEC transfer, CD8 CD45.1+ EECs were analyzed for KLRG1 and CD127 expression. Each condition was repeated at least 2 times. B. Day 14 purified EECs from VSV-OVA infection were transferred into uninfected recipients, and CD8 CD45.1+ EECs in the spleen were analyzed for KLRG1 and CD127 expression 3 or 6 days following transfer. Each condition was repeated at least 2 times.

Mentions: In all of the experiments described above, EECs were sorted 5 days following infection when a large proportion of the antigen-specific cells have this phenotype. Although the population of EECs decreases considerably with time (Fig. 1A and Fig. 6A), we wanted to examine if EECs maintained later in the ongoing immune response still retained their ability to differentiate into SLECs or MPECs. We generated EECs in VSV-OVA infected animals, as in previous experiments, but waited until 14 days after infection to purify and transfer the sorted EECs into new recipients that were infected with either LM-OVA or VSV-OVA. The EECs retained the capacity to robustly differentiate into all of the effector subsets, with LM infection driving plentiful SLEC differentiation and VSV infection driving more MPECs and EECs (Fig. 6B). Interestingly, day 14 VSV EECs, when transferred into uninfected recipients, remained almost entirely EECs 3 or 6 days after transfer (Fig. 6C). These results suggested that as late as 14 days after infection, a small percentage of antigen-specific CD8 T cells that retained the EEC phenotype were still present and failed to exhibit pre-programmed differentiation into SLECs and MPECs.


Early Effector CD8 T Cells Display Plasticity in Populating the Short-Lived Effector and Memory-Precursor Pools Following Bacterial or Viral Infection.

Plumlee CR, Obar JJ, Colpitts SL, Jellison ER, Haining WN, Lefrancois L, Khanna KM - Sci Rep (2015)

With time, EECs lose their ability to generate MPEC and SLEC in the absence of exogenous inflammatory stimuli.A. 14 days following VSV-OVA infection, EECs were purified as in Fig. 2A and transferred into day 2 LM-OVA- or VSV-OVA-infected recipients. 6 days following EEC transfer, CD8 CD45.1+ EECs were analyzed for KLRG1 and CD127 expression. Each condition was repeated at least 2 times. B. Day 14 purified EECs from VSV-OVA infection were transferred into uninfected recipients, and CD8 CD45.1+ EECs in the spleen were analyzed for KLRG1 and CD127 expression 3 or 6 days following transfer. Each condition was repeated at least 2 times.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4507483&req=5

f6: With time, EECs lose their ability to generate MPEC and SLEC in the absence of exogenous inflammatory stimuli.A. 14 days following VSV-OVA infection, EECs were purified as in Fig. 2A and transferred into day 2 LM-OVA- or VSV-OVA-infected recipients. 6 days following EEC transfer, CD8 CD45.1+ EECs were analyzed for KLRG1 and CD127 expression. Each condition was repeated at least 2 times. B. Day 14 purified EECs from VSV-OVA infection were transferred into uninfected recipients, and CD8 CD45.1+ EECs in the spleen were analyzed for KLRG1 and CD127 expression 3 or 6 days following transfer. Each condition was repeated at least 2 times.
Mentions: In all of the experiments described above, EECs were sorted 5 days following infection when a large proportion of the antigen-specific cells have this phenotype. Although the population of EECs decreases considerably with time (Fig. 1A and Fig. 6A), we wanted to examine if EECs maintained later in the ongoing immune response still retained their ability to differentiate into SLECs or MPECs. We generated EECs in VSV-OVA infected animals, as in previous experiments, but waited until 14 days after infection to purify and transfer the sorted EECs into new recipients that were infected with either LM-OVA or VSV-OVA. The EECs retained the capacity to robustly differentiate into all of the effector subsets, with LM infection driving plentiful SLEC differentiation and VSV infection driving more MPECs and EECs (Fig. 6B). Interestingly, day 14 VSV EECs, when transferred into uninfected recipients, remained almost entirely EECs 3 or 6 days after transfer (Fig. 6C). These results suggested that as late as 14 days after infection, a small percentage of antigen-specific CD8 T cells that retained the EEC phenotype were still present and failed to exhibit pre-programmed differentiation into SLECs and MPECs.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Immunology, University of Connecticut Health Center, Farmington, CT.

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.

No MeSH data available.


Related in: MedlinePlus