Manohar, Monali and Hirsh, MarkI and Chen, Yu and Woehrle, Tobias and Karande, Anjali A and Junger, Wolfgang G (2012) ATP release and autocrine signaling through P2X4 receptors regulate gamma delta T cell activation. In: JOURNAL OF LEUKOCYTE BIOLOGY, 92 (4). pp. 787-794.
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Purinergic signaling plays a key role in a variety of physiological functions, including regulation of immune responses. Conventional alpha beta T cells release ATP upon TCR cross-linking; ATP binds to purinergic receptors expressed by these cells and triggers T cell activation in an autocrine and paracrine manner. Here, we studied whether similar purinergic signaling pathways also operate in the ``unconventional'' gamma delta T lymphocytes. We observed that gamma delta T cells purified from peripheral human blood rapidly release ATP upon in vitro stimulation with anti-CD3/CD28-coated beads or IPP. Pretreatment of gamma delta T cells with (10)panx-1, CBX, or Bf A reversed the stimulation-induced increase in extracellular ATP concentration, indicating that panx-1, connexin hemichannels, and vesicular exocytosis contribute to the controlled release of cellular ATP. Blockade of ATP release with (10)panx-1 inhibited Ca2+ signaling in response to TCR stimulation. qPCR revealed that gamma delta T cells predominantly express purinergic receptor subtypes A2a, P2X1, P2X4, P2X7, and P2Y11. We found that pharmacological inhibition of P2X4 receptors with TNP-ATP inhibited transcriptional up-regulation of TNF-alpha and IFN-gamma in gamma delta T cells stimulated with anti-CD3/CD28-coated beads or IPP. Our data thus indicate that purinergic signaling via P2X4 receptors plays an important role in orchestrating the functional response of circulating human gamma delta T cells. J. Leukoc. Biol. 92: 787-794; 2012.
|Item Type:||Journal Article|
|Additional Information:||Copyright for this article belongs to FEDERATION AMER SOC EXP BIOL, USA|
|Department/Centre:||Division of Biological Sciences > Biochemistry|
|Date Deposited:||07 Dec 2012 08:48|
|Last Modified:||18 Dec 2012 12:02|
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