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The acute environment, rather than T cell subset pre-commitment, regulates expression of the human T cell cytokine amphiregulin.

Qi Y, Operario DJ, Georas SN, Mosmann TR - PLoS ONE (2012)

Bottom Line: Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals.Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines.This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.

View Article: PubMed Central - PubMed

Affiliation: David H Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.

ABSTRACT
Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.

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Related in: MedlinePlus

TCR activation induced AR expression in human PBMC T cells.(A) PBMC were treated as indicated and analyzed by ICS. The upper panels show the gating strategy to identify activated (CD69+) CD4 or CD8 T cells expressing AR. The lower panels show the induction of AR by different stimuli in CD4 or CD8 T cells. (B) AR and IL-2 mRNA were measured by RT-PCR in purified CD4 and CD8 T cells after activation by anti-CD3+anti-CD28 beads. Results in (A) and (B) are representative of at least three experiments.
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pone-0039072-g001: TCR activation induced AR expression in human PBMC T cells.(A) PBMC were treated as indicated and analyzed by ICS. The upper panels show the gating strategy to identify activated (CD69+) CD4 or CD8 T cells expressing AR. The lower panels show the induction of AR by different stimuli in CD4 or CD8 T cells. (B) AR and IL-2 mRNA were measured by RT-PCR in purified CD4 and CD8 T cells after activation by anti-CD3+anti-CD28 beads. Results in (A) and (B) are representative of at least three experiments.

Mentions: Human PBMCs were stimulated with soluble anti-CD3+ anti-CD28, SEB, or PMA + ionomycin for 10 hours (protein secretion inhibitors were added during the last 8 hours). CD69 staining increased on almost all anti-CD3/CD28- and P+I-stimulated cells, and a subset of SEB-stimulated cells (Figure 1A). AR staining was increased, only in the CD69+ population, and this increase was most obvious in the P+I-stimulated cells. For all three stimulation conditions, the staining intensity for AR increased for the whole CD69+ population, i.e. separate positive and negative populations were not resolved, and so the percentage of cells in the AR+ gate may be an underestimate of the total number of cells expressing AR. The specificity of AR staining was demonstrated by using a control goat antiserum (right column). Similar results were obtained with CD8 T cells (Figure 1A).


The acute environment, rather than T cell subset pre-commitment, regulates expression of the human T cell cytokine amphiregulin.

Qi Y, Operario DJ, Georas SN, Mosmann TR - PLoS ONE (2012)

TCR activation induced AR expression in human PBMC T cells.(A) PBMC were treated as indicated and analyzed by ICS. The upper panels show the gating strategy to identify activated (CD69+) CD4 or CD8 T cells expressing AR. The lower panels show the induction of AR by different stimuli in CD4 or CD8 T cells. (B) AR and IL-2 mRNA were measured by RT-PCR in purified CD4 and CD8 T cells after activation by anti-CD3+anti-CD28 beads. Results in (A) and (B) are representative of at least three experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375254&req=5

pone-0039072-g001: TCR activation induced AR expression in human PBMC T cells.(A) PBMC were treated as indicated and analyzed by ICS. The upper panels show the gating strategy to identify activated (CD69+) CD4 or CD8 T cells expressing AR. The lower panels show the induction of AR by different stimuli in CD4 or CD8 T cells. (B) AR and IL-2 mRNA were measured by RT-PCR in purified CD4 and CD8 T cells after activation by anti-CD3+anti-CD28 beads. Results in (A) and (B) are representative of at least three experiments.
Mentions: Human PBMCs were stimulated with soluble anti-CD3+ anti-CD28, SEB, or PMA + ionomycin for 10 hours (protein secretion inhibitors were added during the last 8 hours). CD69 staining increased on almost all anti-CD3/CD28- and P+I-stimulated cells, and a subset of SEB-stimulated cells (Figure 1A). AR staining was increased, only in the CD69+ population, and this increase was most obvious in the P+I-stimulated cells. For all three stimulation conditions, the staining intensity for AR increased for the whole CD69+ population, i.e. separate positive and negative populations were not resolved, and so the percentage of cells in the AR+ gate may be an underestimate of the total number of cells expressing AR. The specificity of AR staining was demonstrated by using a control goat antiserum (right column). Similar results were obtained with CD8 T cells (Figure 1A).

Bottom Line: Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals.Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines.This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.

View Article: PubMed Central - PubMed

Affiliation: David H Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.

ABSTRACT
Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses.

Show MeSH
Related in: MedlinePlus