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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

Whole genome microarray studies reveal a subset of genes differentially expressed in EECs generated after LM versus VSV infection.A. mRNA Expression levels were measured by microarray analysis with Illumina BeadChips of sorted EECs, as in Fig. 2A, 5 days following LM-OVA or VSV-OVA infection. The top 50 and bottom 50 differentially regulated genes, ranked by signal-to-noise, are displayed. Each row represents an individual sample. B. The AVG signal from the microarray of LM or VSV EECs for selected MPEC genes is graphed. C. Enrichment profile generated from GSEA using the top 50 genes enriched in VSV EECs compared to a gene set generated with IL-7RHi (MPEC) and IL-7RLo (SLEC) samples. Genes identified as being enriched in both VSV EECs and IL-7RHi cells (MPECs) are marked with a red asterisk in part A.
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f3: Whole genome microarray studies reveal a subset of genes differentially expressed in EECs generated after LM versus VSV infection.A. mRNA Expression levels were measured by microarray analysis with Illumina BeadChips of sorted EECs, as in Fig. 2A, 5 days following LM-OVA or VSV-OVA infection. The top 50 and bottom 50 differentially regulated genes, ranked by signal-to-noise, are displayed. Each row represents an individual sample. B. The AVG signal from the microarray of LM or VSV EECs for selected MPEC genes is graphed. C. Enrichment profile generated from GSEA using the top 50 genes enriched in VSV EECs compared to a gene set generated with IL-7RHi (MPEC) and IL-7RLo (SLEC) samples. Genes identified as being enriched in both VSV EECs and IL-7RHi cells (MPECs) are marked with a red asterisk in part A.

Mentions: Our results suggested that EECs were committed to a downstream fate based on signals received in different infectious environments. Therefore, we examined genetic differences between VSV and LM EECs to identify genes enriched within VSV EECs that may be important for MPEC generation and genes enriched within the LM EECs that may be important for SLEC differentiation. RNA was isolated from purified EECs sorted from either VSV- or LM- infected mice, and used for whole-genome analysis with Illumina BeadChips. We found 53 genes that were 2-fold higher in VSV EECs compared to LM EECs and 63 genes at least 2-fold higher in LM EECs compared to VSV EECs. Figure 3A shows the top 50 upregulated or downregulated genes, ranked by the signal-to-noise metric. We first looked at genes from the literature known to be important for MPEC or SLEC development125. Figure 3B shows an example of 5 MPEC genes that were enriched in VSV EECs, which hints at a correlation between VSV EECs 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)

Whole genome microarray studies reveal a subset of genes differentially expressed in EECs generated after LM versus VSV infection.A. mRNA Expression levels were measured by microarray analysis with Illumina BeadChips of sorted EECs, as in Fig. 2A, 5 days following LM-OVA or VSV-OVA infection. The top 50 and bottom 50 differentially regulated genes, ranked by signal-to-noise, are displayed. Each row represents an individual sample. B. The AVG signal from the microarray of LM or VSV EECs for selected MPEC genes is graphed. C. Enrichment profile generated from GSEA using the top 50 genes enriched in VSV EECs compared to a gene set generated with IL-7RHi (MPEC) and IL-7RLo (SLEC) samples. Genes identified as being enriched in both VSV EECs and IL-7RHi cells (MPECs) are marked with a red asterisk in part A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Whole genome microarray studies reveal a subset of genes differentially expressed in EECs generated after LM versus VSV infection.A. mRNA Expression levels were measured by microarray analysis with Illumina BeadChips of sorted EECs, as in Fig. 2A, 5 days following LM-OVA or VSV-OVA infection. The top 50 and bottom 50 differentially regulated genes, ranked by signal-to-noise, are displayed. Each row represents an individual sample. B. The AVG signal from the microarray of LM or VSV EECs for selected MPEC genes is graphed. C. Enrichment profile generated from GSEA using the top 50 genes enriched in VSV EECs compared to a gene set generated with IL-7RHi (MPEC) and IL-7RLo (SLEC) samples. Genes identified as being enriched in both VSV EECs and IL-7RHi cells (MPECs) are marked with a red asterisk in part A.
Mentions: Our results suggested that EECs were committed to a downstream fate based on signals received in different infectious environments. Therefore, we examined genetic differences between VSV and LM EECs to identify genes enriched within VSV EECs that may be important for MPEC generation and genes enriched within the LM EECs that may be important for SLEC differentiation. RNA was isolated from purified EECs sorted from either VSV- or LM- infected mice, and used for whole-genome analysis with Illumina BeadChips. We found 53 genes that were 2-fold higher in VSV EECs compared to LM EECs and 63 genes at least 2-fold higher in LM EECs compared to VSV EECs. Figure 3A shows the top 50 upregulated or downregulated genes, ranked by the signal-to-noise metric. We first looked at genes from the literature known to be important for MPEC or SLEC development125. Figure 3B shows an example of 5 MPEC genes that were enriched in VSV EECs, which hints at a correlation between VSV EECs 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