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.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Abstract / Bemerkung
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.
Stichworte
cell activation; T cells; T-cell receptor; signal transduction
Erscheinungsjahr
2009
Zeitschriftentitel
IMMUNOLOGY
Band
128
Ausgabe
1pt2
Seite(n)
e728-e737
ISSN
0019-2805
eISSN
1365-2567
Page URI
https://pub.uni-bielefeld.de/record/1591412

Zitieren

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. doi:10.1111/j.1365-2567.2009.03075.x
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.

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