P2X4 and P2X7 are essential players in basal T cell activity and Ca2+ signaling milliseconds after T cell activation.

Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca2+ microdomains. Purinergic signaling is known to be involved in Ca2+ influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca2+ live-cell imaging system, we show that the two purinergic cation channels P2X4 and P2X7 not only are involved in the global Ca2+ signals but also promote initial Ca2+ microdomains tens of milliseconds after T cell stimulation. These Ca2+ microdomains were significantly decreased in T cells from P2rx4-/- and P2rx7-/- mice or by pharmacological inhibition or blocking. Furthermore, we show a pannexin-1-dependent activation of P2X4 in the absence of T cell receptor/CD3 stimulation. Subsequently, upon T cell receptor/CD3 stimulation, ATP release is increased and autocrine activation of both P2X4 and P2X7 then amplifies initial Ca2+ microdomains already in the first second of T cell activation.