Murine neonatal CD4+ cells are poised for rapid Th2 effector-like function.
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 IL-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.
Rose
Shawn
S
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, 1600 NW 10th Avenue, Miami, FL 33136, USA.
Lichtenheld
Mathias
M
Foote
Monica R
MR
Adkins
Becky
B
D000818:Animals; D000831:Animals, Newborn; D018899:CpG Islands / Q000235:genetics / Q000276:immunology*; D019175:DNA Methylation; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4