Lymphocytes from P2X₇-deficient mice exhibit enhanced P2X ₇ responses

The purinergic receptor P2X₇ is expressed on immune cells, and its stimulation results in the release of IL-1β from macrophages. Its absence, as evidenced from the analysis of two independent strains of P2X ₇-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, although its function and even its presence in these cells are highly contested, with anti-P2X₇ antibodies 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 antibody recognition epitopes to P2X₇ and some properties of the genuine receptor. In this study, we show that whereas P2X₇ activity is absent from macrophages and dendritic cells in P2X₇^-/- animals, T cells from one gene-deficient strain unexpectedly 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^-/- animals is discussed, as is the implication that the immune and indeed neuronal functions of P2X₇ may have been underestimated.