Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses

Abstract: The purinergic receptor P2X7 is ex-pressed on immune cells, and its stimulation results in the release of IL-1 from macrophages. Its ab-sence, as evidenced from the analysis of two inde-pendent strains of P2X7-deficient mice, results in reduced susceptibility to inflammatory disease, and the molecule is an important, potential therapeutic target in autoimmunity. However, P2X7 has also been detected in several neuronal cell types, al-though its function and even its presence in these cells are highly contested, with anti-P2X7 antibod-ies staining brain tissue from both strains of P2X7 / mice identically to wild-type mice. It has therefore been suggested that neurons express a distinct “P2X7-like ” protein that has similar anti-body recognition epitopes to P2X7 and some prop-erties of the genuine receptor. In this study, we show that whereas P2X7 activity is absent from macrophages and dendritic cells in P2X7 / ani-mals, T cells from one gene-deficient strain unex-pectedly exhibit higher levels of P2X7 activity than that found in cells from control, unmanipulated C57BL/6 mice. A potential mechanism for this tissue-specific P2X7 expression in P2X7 / ani-mals is discussed, as is the implication that the immune and indeed neuronal functions of P2X7 may have been underestimated. J. Leukoc. Biol