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Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling

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Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. / Linnemann, Carsten; Schildberg, Frank A; Schurich, Anna; Diehl, Linda; Hegenbarth, Silke I; Endl, Elmar; Lacher, Svenja; Müller, Christa E; Frey, Jürgen; Simeoni, Luca; Schraven, Burkhart; Stabenow, Dirk; Knolle, Percy A.

in: IMMUNOLOGY, Jahrgang 128, Nr. 1 Suppl, 09.2009, S. e728-37.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Linnemann, C, Schildberg, FA, Schurich, A, Diehl, L, Hegenbarth, SI, Endl, E, Lacher, S, Müller, CE, Frey, J, Simeoni, L, Schraven, B, Stabenow, D & Knolle, PA 2009, 'Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling', IMMUNOLOGY, Jg. 128, Nr. 1 Suppl, S. e728-37. https://doi.org/10.1111/j.1365-2567.2009.03075.x

APA

Linnemann, C., Schildberg, F. A., Schurich, A., Diehl, L., Hegenbarth, S. I., Endl, E., Lacher, S., Müller, C. E., Frey, J., Simeoni, L., Schraven, B., Stabenow, D., & Knolle, P. A. (2009). Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY, 128(1 Suppl), e728-37. https://doi.org/10.1111/j.1365-2567.2009.03075.x

Vancouver

Linnemann C, Schildberg FA, Schurich A, Diehl L, Hegenbarth SI, Endl E et al. Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY. 2009 Sep;128(1 Suppl):e728-37. https://doi.org/10.1111/j.1365-2567.2009.03075.x

Bibtex

@article{191a42f7319144bdae5c6fc9796896df,
title = "Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling",
abstract = "Adenosine is a well-described anti-inflammatory modulator of immune responses within peripheral tissues. Extracellular adenosine accumulates in inflamed and damaged tissues and inhibits the effector functions of various immune cell populations, including CD8 T cells. However, it remains unclear whether extracellular adenosine also regulates the initial activation of na{\"i}ve CD8 T cells by professional and semi-professional antigen-presenting cells, which determines their differentiation into effector or tolerant CD8 T cells, respectively. We show that adenosine inhibited the initial activation of murine na{\"i}ve CD8 T cells after alphaCD3/CD28-mediated stimulation. Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of na{\"i}ve CD8 T cells. Remarkably, adenosine interfered efficiently with CD8 T-cell priming by professional antigen-presenting cells (dendritic cells) and semi-professional antigen-presenting cells (liver sinusoidal endothelial cells). Further analysis of the underlying mechanisms demonstrated that adenosine prevented rapid tyrosine phosphorylation of the key kinase ZAP-70 as well as Akt and ERK1/2 in na{\"i}ve alphaCD3/CD28-stimulated CD8 cells. Consequently, alphaCD3/CD28-induced calcium-influx into CD8 cells was reduced by exposure to adenosine. Our results support the notion that extracellular adenosine controls membrane-proximal T-cell receptor signalling and thereby also differentiation of na{\"i}ve CD8 T cells. These data raise the possibility that extracellular adenosine has a physiological role in the regulation of CD8 T-cell priming and differentiation in peripheral organs.",
keywords = "Adenosine, Animals, Anti-Inflammatory Agents, Non-Steroidal, Antigen-Presenting Cells, Antigens, CD28, Antigens, CD3, CD8-Positive T-Lymphocytes, Calcium, Cell Differentiation, Immunologic Factors, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Protein Kinases, Receptors, Antigen, T-Cell, Signal Transduction",
author = "Carsten Linnemann and Schildberg, {Frank A} and Anna Schurich and Linda Diehl and Hegenbarth, {Silke I} and Elmar Endl and Svenja Lacher and M{\"u}ller, {Christa E} and J{\"u}rgen Frey and Luca Simeoni and Burkhart Schraven and Dirk Stabenow and Knolle, {Percy A}",
year = "2009",
month = sep,
doi = "10.1111/j.1365-2567.2009.03075.x",
language = "English",
volume = "128",
pages = "e728--37",
journal = "IMMUNOLOGY",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "1 Suppl",

}

RIS

TY - JOUR

T1 - Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling

AU - Linnemann, Carsten

AU - Schildberg, Frank A

AU - Schurich, Anna

AU - Diehl, Linda

AU - Hegenbarth, Silke I

AU - Endl, Elmar

AU - Lacher, Svenja

AU - Müller, Christa E

AU - Frey, Jürgen

AU - Simeoni, Luca

AU - Schraven, Burkhart

AU - Stabenow, Dirk

AU - Knolle, Percy A

PY - 2009/9

Y1 - 2009/9

N2 - Adenosine is a well-described anti-inflammatory modulator of immune responses within peripheral tissues. Extracellular adenosine accumulates in inflamed and damaged tissues and inhibits the effector functions of various immune cell populations, including CD8 T cells. However, it remains unclear whether extracellular adenosine also regulates the initial activation of naïve CD8 T cells by professional and semi-professional antigen-presenting cells, which determines their differentiation into effector or tolerant CD8 T cells, respectively. We show that adenosine inhibited the initial activation of murine naïve CD8 T cells after alphaCD3/CD28-mediated stimulation. Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of naïve CD8 T cells. Remarkably, adenosine interfered efficiently with CD8 T-cell priming by professional antigen-presenting cells (dendritic cells) and semi-professional antigen-presenting cells (liver sinusoidal endothelial cells). Further analysis of the underlying mechanisms demonstrated that adenosine prevented rapid tyrosine phosphorylation of the key kinase ZAP-70 as well as Akt and ERK1/2 in naïve alphaCD3/CD28-stimulated CD8 cells. Consequently, alphaCD3/CD28-induced calcium-influx into CD8 cells was reduced by exposure to adenosine. Our results support the notion that extracellular adenosine controls membrane-proximal T-cell receptor signalling and thereby also differentiation of naïve CD8 T cells. These data raise the possibility that extracellular adenosine has a physiological role in the regulation of CD8 T-cell priming and differentiation in peripheral organs.

AB - Adenosine is a well-described anti-inflammatory modulator of immune responses within peripheral tissues. Extracellular adenosine accumulates in inflamed and damaged tissues and inhibits the effector functions of various immune cell populations, including CD8 T cells. However, it remains unclear whether extracellular adenosine also regulates the initial activation of naïve CD8 T cells by professional and semi-professional antigen-presenting cells, which determines their differentiation into effector or tolerant CD8 T cells, respectively. We show that adenosine inhibited the initial activation of murine naïve CD8 T cells after alphaCD3/CD28-mediated stimulation. Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of naïve CD8 T cells. Remarkably, adenosine interfered efficiently with CD8 T-cell priming by professional antigen-presenting cells (dendritic cells) and semi-professional antigen-presenting cells (liver sinusoidal endothelial cells). Further analysis of the underlying mechanisms demonstrated that adenosine prevented rapid tyrosine phosphorylation of the key kinase ZAP-70 as well as Akt and ERK1/2 in naïve alphaCD3/CD28-stimulated CD8 cells. Consequently, alphaCD3/CD28-induced calcium-influx into CD8 cells was reduced by exposure to adenosine. Our results support the notion that extracellular adenosine controls membrane-proximal T-cell receptor signalling and thereby also differentiation of naïve CD8 T cells. These data raise the possibility that extracellular adenosine has a physiological role in the regulation of CD8 T-cell priming and differentiation in peripheral organs.

KW - Adenosine

KW - Animals

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Antigen-Presenting Cells

KW - Antigens, CD28

KW - Antigens, CD3

KW - CD8-Positive T-Lymphocytes

KW - Calcium

KW - Cell Differentiation

KW - Immunologic Factors

KW - Lymphocyte Activation

KW - Mice

KW - Mice, Inbred C57BL

KW - Protein Kinases

KW - Receptors, Antigen, T-Cell

KW - Signal Transduction

U2 - 10.1111/j.1365-2567.2009.03075.x

DO - 10.1111/j.1365-2567.2009.03075.x

M3 - SCORING: Journal article

C2 - 19740334

VL - 128

SP - e728-37

JO - IMMUNOLOGY

JF - IMMUNOLOGY

SN - 0019-2805

IS - 1 Suppl

ER -