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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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AR is produced by T cell subsets expressing different chemokine receptors and surface markers.PBMC were treated with medium alone, anti-CD3+ anti-CD28 antibodies, or SEB in the presence of TAPI-1 for 8 hours. Cells were stained for AR and cell-surface markers and analyzed by flow cytometry. Representative of two experiments.
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pone-0039072-g006: AR is produced by T cell subsets expressing different chemokine receptors and surface markers.PBMC were treated with medium alone, anti-CD3+ anti-CD28 antibodies, or SEB in the presence of TAPI-1 for 8 hours. Cells were stained for AR and cell-surface markers and analyzed by flow cytometry. Representative of two experiments.

Mentions: Chemokine receptors expressed selectively by T cell subsets lead to different homing and chemotactic properties. Expression patterns of chemokine receptors are partly but not entirely related to cytokine commitment patterns [36]–[39]. Additional surface markers, including CD27 and the homing receptor CD62L are also expressed heterogeneously on human CD4 T cells. We therefore examined AR expression within subsets of memory CD4 T cells defined by the expression of these proteins. AR was produced at approximately similar frequencies by CD4 T cells positive or negative for the chemokine receptors CCR4, CCR7, CXCR3 and CXCR5, as well as CD62L and CD27 (Figure 6). However, expression of the activation-induced protein CD69 was strongly correlated with AR expression, as seen in previous figures. Taken together with the data described above, AR expression appears to be a general ability of most or all subtypes of human T cells after TCR activation.


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)

AR is produced by T cell subsets expressing different chemokine receptors and surface markers.PBMC were treated with medium alone, anti-CD3+ anti-CD28 antibodies, or SEB in the presence of TAPI-1 for 8 hours. Cells were stained for AR and cell-surface markers and analyzed by flow cytometry. Representative of two experiments.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0039072-g006: AR is produced by T cell subsets expressing different chemokine receptors and surface markers.PBMC were treated with medium alone, anti-CD3+ anti-CD28 antibodies, or SEB in the presence of TAPI-1 for 8 hours. Cells were stained for AR and cell-surface markers and analyzed by flow cytometry. Representative of two experiments.
Mentions: Chemokine receptors expressed selectively by T cell subsets lead to different homing and chemotactic properties. Expression patterns of chemokine receptors are partly but not entirely related to cytokine commitment patterns [36]–[39]. Additional surface markers, including CD27 and the homing receptor CD62L are also expressed heterogeneously on human CD4 T cells. We therefore examined AR expression within subsets of memory CD4 T cells defined by the expression of these proteins. AR was produced at approximately similar frequencies by CD4 T cells positive or negative for the chemokine receptors CCR4, CCR7, CXCR3 and CXCR5, as well as CD62L and CD27 (Figure 6). However, expression of the activation-induced protein CD69 was strongly correlated with AR expression, as seen in previous figures. Taken together with the data described above, AR expression appears to be a general ability of most or all subtypes of human T cells after TCR activation.

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