The Extracellular ATP Receptor P2RX7 Imprints a Promemory Transcriptional Signature in Effector CD8+ T Cells

Trupti Vardam-Kaur, Sarah van Dijk, Changwei Peng, Kelsey M. Wanhainen, Stephen C. Jameson, Henrique Borges da Silva

Research output: Contribution to journalArticlepeer-review

Abstract

Development of CD8+ central memory T (Tcm) and resident memory T (Trm) cells, which promote immunity in the circulation and in barrier tissues, respectively, is not completely understood. Tcm and Trm cells may arise from common precursors; however, their fate-inducing signals are elusive. We found that virus-specific effector CD8+ T cells display heterogeneous expression of the extracellular ATP sensor P2RX7. P2RX7-high expression is confined, at peak effector phase, to CD62L+ memory precursors, which preferentially form Tcm cells. Among early effector CD8+ T cells, asymmetrical P2RX7 distribution correlated with distinct transcriptional signatures, with P2RX7-high cells enriched for memory and tissue residency sets. P2RX7-high early effectors preferentially form both Tcm and Trm cells. Defective Tcm and Trm cell formation in P2RX7 deficiency is significantly reverted when the transcriptional repressor Zeb2 is ablated. Mechanistically, P2RX7 negatively regulates Zeb2 expression, at least partially through TGF-β sensing in early effector CD8+ T cells. Our study indicates that unequal P2RX7 upregulation in effector CD8+ T cells is a foundational element of the early Tcm/Trm fate.

Original languageEnglish (US)
Pages (from-to)1686-1699
Number of pages14
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume208
Issue number7
DOIs
StatePublished - Apr 1 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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