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

Linnemann C, Schildberg FA, Schurich A, Diehl L, Hegenbarth SI, Endl E, Lacher S, Mueller CE, Frey J, Simeoni L, Schraven B, et al. (2009)
IMMUNOLOGY 128(1pt2): e728-e737.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ; ; ; ; ; ;
All
Abstract
P>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 naive 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 naive CD8 T cells after alpha CD3/CD28-mediated stimulation. Adenosine caused inhibition of activation, cytokine production, metabolic activity, proliferation and ultimately effector differentiation of naive 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 naive alpha CD3/CD28-stimulated CD8 cells. Consequently, alpha CD3/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 naive 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.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Linnemann C, Schildberg FA, Schurich A, et al. Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY. 2009;128(1pt2):e728-e737.
Linnemann, C., Schildberg, F. A., Schurich, A., Diehl, L., Hegenbarth, S. I., Endl, E., Lacher, S., et al. (2009). Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY, 128(1pt2), e728-e737.
Linnemann, C., Schildberg, F. A., Schurich, A., Diehl, L., Hegenbarth, S. I., Endl, E., Lacher, S., Mueller, C. E., Frey, J., Simeoni, L., et al. (2009). Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY 128, e728-e737.
Linnemann, C., et al., 2009. Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY, 128(1pt2), p e728-e737.
C. Linnemann, et al., “Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling”, IMMUNOLOGY, vol. 128, 2009, pp. e728-e737.
Linnemann, C., Schildberg, F.A., Schurich, A., Diehl, L., Hegenbarth, S.I., Endl, E., Lacher, S., Mueller, C.E., Frey, J., Simeoni, L., Schraven, B., Stabenow, D., Knolle, P.A.: Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling. IMMUNOLOGY. 128, e728-e737 (2009).
Linnemann, Carsten, Schildberg, Frank A., Schurich, Anna, Diehl, Linda, Hegenbarth, Silke I., Endl, Elmar, Lacher, Svenja, Mueller, Christa E., Frey, Jürgen, Simeoni, Luca, Schraven, Burkhart, Stabenow, Dirk, and Knolle, Percy A. “Adenosine regulates CD8 T-cell priming by inhibition of membrane-proximal T-cell receptor signalling”. IMMUNOLOGY 128.1pt2 (2009): e728-e737.
This data publication is cited in the following publications:
This publication cites the following data publications:

10 Citations in Europe PMC

Data provided by Europe PubMed Central.

NADH oxidase-dependent CD39 expression by CD8(+) T cells modulates interferon gamma responses via generation of adenosine.
Bai A, Moss A, Rothweiler S, Longhi MS, Wu Y, Junger WG, Robson SC., Nat Commun 6(), 2015
PMID: 26549640
T Lymphocyte Inhibition by Tumor-Infiltrating Dendritic Cells Involves Ectonucleotidase CD39 but Not Arginase-1.
Trad M, Gautheron A, Fraszczak J, Alizadeh D, Larmonier C, LaCasse CJ, Centuori S, Audia S, Samson M, Ciudad M, Bonnefoy F, Lemaire-Ewing S, Katsanis E, Perruche S, Saas P, Bonnotte B., Biomed Res Int 2015(), 2015
PMID: 26491691
Adenosine signalling in diabetes mellitus--pathophysiology and therapeutic considerations.
Antonioli L, Blandizzi C, Csoka B, Pacher P, Hasko G., Nat Rev Endocrinol 11(4), 2015
PMID: 25687993
Extracellular adenosine-mediated modulation of regulatory T cells.
Ohta A, Sitkovsky M., Front Immunol 5(), 2014
PMID: 25071765
Targeting CD73 and downstream adenosine receptor signaling in triple-negative breast cancer.
Allard B, Turcotte M, Stagg J., Expert Opin. Ther. Targets 18(8), 2014
PMID: 24798880
Regulation of lymphocyte function by adenosine.
Linden J, Cekic C., Arterioscler. Thromb. Vasc. Biol. 32(9), 2012
PMID: 22772752
Immunological alterations mediated by adenosine during host-microbial interactions.
Drygiannakis I, Ernst PB, Lowe D, Glomski IJ., Immunol. Res. 50(1), 2011
PMID: 21479929

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 19740334
PubMed | Europe PMC

Search this title in

Google Scholar