title: High sensitivity of intestinal CD8+ T cells to nucleotides indicates P2X7 as a regulator for intestinal T cell responses.
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.
authors.affiliation: Institute for Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Heiss
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jänner
authors.forename: Birgit
authors.initials: B
authors.lastname: Mähnss
authors.forename: Valéa
authors.initials: V
authors.lastname: Schumacher
authors.forename: Friedrich
authors.initials: F
authors.lastname: Koch-Nolte
authors.forename: Friedrich
authors.initials: F
authors.lastname: Haag
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Mittrücker