ABSTRACT
The purinoreceptor P2X7 is expressed on subsets of T cells and mediates responses of these cells to extracellular nucleotides such as ATP or NAD(+). We identified P2X7 as a molecule highly up-regulated on conventional CD8alphabeta(+) and unconventional CD8alphaalpha(+) T cells of the intestinal epithelium of mice. In contrast, CD8(+) T cells derived from spleen, mesenteric lymph nodes, and liver expressed only marginal levels of P2X7. However, P2X7 was highly up-regulated on CD8(+) T cells from spleen and lymph nodes when T cells were activated in the presence of retinoic acid. High P2X7 expression on intestinal CD8(+) T cells as well as on CD8(+) T cells incubated with retinoic acid resulted in enhanced sensitivity of cells to extracellular nucleotides. Both cell populations showed a high level of apoptosis following incubation with NAD(+) and the ATP derivative 2',3'-O-(benzoyl-4-benzoyl)-ATP, and injection of NAD(+) caused selective in vivo depletion of intestinal CD8(+) T cells. Following oral infection with Listeria monocytogenes, P2X7-deficient mice showed similar CD8(+) T cell responses in the spleen, but enhanced responses in the intestinal mucosa, when compared with similarly treated wild-type control mice. Overall, our observations define P2X7 as a new regulatory element in the control of CD8(+) T cell responses in the intestinal mucosa.
Subject(s)
Adenosine Diphosphate/analogs & derivatives , CD8-Positive T-Lymphocytes/immunology , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , NAD/administration & dosage , Receptors, Purinergic P2/physiology , ADP Ribose Transferases/biosynthesis , ADP Ribose Transferases/physiology , Adenosine Diphosphate/administration & dosage , Adenosine Diphosphate/pharmacology , Animals , Apoptosis/drug effects , Apoptosis/immunology , CD8-Positive T-Lymphocytes/enzymology , CD8-Positive T-Lymphocytes/metabolism , Dose-Response Relationship, Immunologic , Intestinal Mucosa/drug effects , Intestinal Mucosa/enzymology , Mice , Mice, Inbred C57BL , Mice, Knockout , NAD/pharmacology , Receptors, Purinergic P2/biosynthesis , Receptors, Purinergic P2/deficiency , Receptors, Purinergic P2X7 , T-Lymphocyte Subsets/enzymology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Up-Regulation/drug effects , Up-Regulation/immunologyABSTRACT
Secreted lipases of Candida albicans are encoded by a gene family with at least 10 members (LIP1-LIP10). The expression pattern of this multigene family was investigated using reverse transcription polymerase chain reaction in experimental infections and in samples of patients suffering from oral candidosis. The findings illustrate that individual lipase genes are differentially regulated in a mouse model of systemic candidosis with some members showing sustained expression and others being transiently expressed or even silent. The lipase gene expression profile depended on the stage of infection rather than on the organ localization. This temporal regulation of lipase gene expression was also detected in an experimental model of oral candidosis. Furthermore, the expression of candidal lipase genes in human specimens is shown for the first time.