Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function

Shawn Rose, Mathias Lichtenheld, Monica R. Foote, Becky Adkins

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Murine neonates typically mount Th2-biased immune responses. This entails a cell-intrinsic component whose molecular basis is unknown. We found that neonatal CD4+ T cells are uniquely poised for rapid Th2 function. Within 24 h of activation, neonatal CD4+ cells made high levels of IL-4 and IL-13 mRNA and protein. The rapid high-level IL-4 production arose from a small subpopulation of cells, did not require cell cycle entry, and was unaffected by pharmacologic DNA demethylation. CpG methylation analyses in resting neonatal cells revealed pre-existing hypomethylation at a key Th2 cytokine regulatory region, termed conserved noncoding sequence 1 (CNS-1). Robust Th2 function and increased CNS-1 demethylation was a stable property that persisted in neonatal Th2 effectors. The transcription factor STAT6 was not required for CNS-1 demethylation and this state was already established in neonatal CD4 single-positive thymocytes. CNS-1 demethylation levels were much greater in EL-4-expressing CD4 single-positive thymocytes compared with unactivated cells. Together, these results indicate that neonatal CD4 + T cells possess distinct qualities that could predispose them toward rapid, effector-like Th2 function.

Original languageEnglish (US)
Pages (from-to)2667-2678
Number of pages12
JournalJournal of Immunology
Volume178
Issue number5
DOIs
StatePublished - Mar 1 2007

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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