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

Initial T cell activation is triggered by the formation of highly dynamic, spatiotemporally restricted Ca microdomains. Purinergic signaling is known to be involved in Ca influx in T cells at later stages compared to the initial microdomain formation. Using a high-resolution Ca live-cell imaging system, we show that the two purinergic cation channels P2X4 and P2X7 not only are involved in the global Ca signals but also promote initial Ca microdomains tens of milliseconds after T cell stimulation. These Ca microdomains were significantly decreased in T cells from and 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 Ca microdomains already in the first second of T cell activation.