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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

EECs transferred into infected mice show plasticity by modulating their differentiation according to the infection-induced inflammatory environment of the recipient mouse.A. EECs were purified, as described in Fig. 2A, following LM-OVA or VSV-OVA infection and transferred into LM-OVA infected recipients that had been infected for 2 days. 6 days following the EEC transfer, CD8+ CD45.1+ transferred EECs in the spleen were analyzed for KLRG1 and CD127. Percentages of SLECs, MPECs, and EECs are graphed for both LM-OVA EECs and VSV-OVA EECs from 3–4 mice. This data is representative of at least 2 experiments. B. Same as A, except recipient mice were infected with VSV-OVA 2 days prior to EEC transfer.
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f4: EECs transferred into infected mice show plasticity by modulating their differentiation according to the infection-induced inflammatory environment of the recipient mouse.A. EECs were purified, as described in Fig. 2A, following LM-OVA or VSV-OVA infection and transferred into LM-OVA infected recipients that had been infected for 2 days. 6 days following the EEC transfer, CD8+ CD45.1+ transferred EECs in the spleen were analyzed for KLRG1 and CD127. Percentages of SLECs, MPECs, and EECs are graphed for both LM-OVA EECs and VSV-OVA EECs from 3–4 mice. This data is representative of at least 2 experiments. B. Same as A, except recipient mice were infected with VSV-OVA 2 days prior to EEC transfer.

Mentions: In the absence of inflammation, EECs proved committed to a fate initially programmed by the infectious setting. To test if the commitment of EECs towards an MPEC or SLEC fate was maintained in the presence of additional exogenous stimuli, EECs were again purified 5 days after LM-OVA or VSV-OVA infection (as in Fig. 2A), but sorted cells were transferred into recipients that had been infected with LM-OVA or VSV-OVA 2 days before. Under these conditions both antigen and inflammation are high in the recipient mice. The transferred cells were then examined 6 days after transfer in the infected recipients (i.e. day 8 after initial infection). Unlike our earlier results, both LM EECs and VSV EECs formed robust populations of SLECs when transferred into LM-infected recipients (Fig. 4A). The opposite was found when LM EECs or VSV EECs were transferred into VSV-infected recipients (Fig. 4B) where both formed significantly more EECs and MPECs (compared to the LM recipients), with LM EECs forming slightly more MPECs. In both conditions, the source of the EECs had little to no effect on the downstream phenotype of the transferred OT-I CD8 T cells. Conversely the environmental setting driven by the type of infection in the recipient animals was critical for regulating cellular differentiation. These results suggest that although EECs may be pre-programmed to form SLECs or MPECs when transferred into uninfected recipients, their capacity to form either subset remains intact when provided the necessary environmental signals to re-direct differentiation.


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)

EECs transferred into infected mice show plasticity by modulating their differentiation according to the infection-induced inflammatory environment of the recipient mouse.A. EECs were purified, as described in Fig. 2A, following LM-OVA or VSV-OVA infection and transferred into LM-OVA infected recipients that had been infected for 2 days. 6 days following the EEC transfer, CD8+ CD45.1+ transferred EECs in the spleen were analyzed for KLRG1 and CD127. Percentages of SLECs, MPECs, and EECs are graphed for both LM-OVA EECs and VSV-OVA EECs from 3–4 mice. This data is representative of at least 2 experiments. B. Same as A, except recipient mice were infected with VSV-OVA 2 days prior to EEC transfer.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: EECs transferred into infected mice show plasticity by modulating their differentiation according to the infection-induced inflammatory environment of the recipient mouse.A. EECs were purified, as described in Fig. 2A, following LM-OVA or VSV-OVA infection and transferred into LM-OVA infected recipients that had been infected for 2 days. 6 days following the EEC transfer, CD8+ CD45.1+ transferred EECs in the spleen were analyzed for KLRG1 and CD127. Percentages of SLECs, MPECs, and EECs are graphed for both LM-OVA EECs and VSV-OVA EECs from 3–4 mice. This data is representative of at least 2 experiments. B. Same as A, except recipient mice were infected with VSV-OVA 2 days prior to EEC transfer.
Mentions: In the absence of inflammation, EECs proved committed to a fate initially programmed by the infectious setting. To test if the commitment of EECs towards an MPEC or SLEC fate was maintained in the presence of additional exogenous stimuli, EECs were again purified 5 days after LM-OVA or VSV-OVA infection (as in Fig. 2A), but sorted cells were transferred into recipients that had been infected with LM-OVA or VSV-OVA 2 days before. Under these conditions both antigen and inflammation are high in the recipient mice. The transferred cells were then examined 6 days after transfer in the infected recipients (i.e. day 8 after initial infection). Unlike our earlier results, both LM EECs and VSV EECs formed robust populations of SLECs when transferred into LM-infected recipients (Fig. 4A). The opposite was found when LM EECs or VSV EECs were transferred into VSV-infected recipients (Fig. 4B) where both formed significantly more EECs and MPECs (compared to the LM recipients), with LM EECs forming slightly more MPECs. In both conditions, the source of the EECs had little to no effect on the downstream phenotype of the transferred OT-I CD8 T cells. Conversely the environmental setting driven by the type of infection in the recipient animals was critical for regulating cellular differentiation. These results suggest that although EECs may be pre-programmed to form SLECs or MPECs when transferred into uninfected recipients, their capacity to form either subset remains intact when provided the necessary environmental signals to re-direct differentiation.

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