Molecular mechanisms of extracellular adenine nucleotides-mediated inhibition of human Cd4(+) T lymphocytes activation.
We have previously reported that ATPgammaS, a slowly hydrolyzed analog of ATP, inhibits the activation of human CD4(+) T lymphocytes by anti-CD3 and anti-CD28 mAb. In this report we have partially characterized the signaling mechanisms involved in this immunosuppressive effect. ATPgammaS had no inhibitory effect on CD4(+) T-cell activation induced by PMA and anti-CD28, indicating that it acts proximally to the TCR. It had no effect on the calcium rise induced by CD3/CD28 stimulation, but inhibited the phosphorylation of three kinases, ERK2, p38 MAPK and PKB, that play a key role in the activation of T cells. The receptor involved in these actions remains unidentified.
Duhant
Xavier
X
Institute of Interdisciplinary Research, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Suarez Gonzalez
Nathalie
N
Schandené
Liliane
L
Goldman
Michel
M
Communi
Didier
D
Boeynaems
Jean-Marie
JM