CD4+ T cells from human neonates and infants are poised spontaneously to run a nonclassical IL-4 program.
Senescence or biological aging impacts a vast variety of molecular and cellular processes. To date, it is unknown whether CD4(+) Th cells display an age-dependent bias for development into specific subpopulations. In this study, we show the appearance of a distinct CD4(+) T cell subset expressing IL-4 at an early stage of development in infant adenoids and cord blood that is lost during aging. We identified by flow cytometric, fluorescent microscopic, immunoblot, and mass spectrometric analysis a population of CD4(+) T cells that expressed an unglycosylated isoform of IL-4. This T cell subpopulation was found in neonatal but not in adult CD4(+) T cells. Furthermore, we show that the mRNA of the Th2 master transcription factor GATA3 is preferentially expressed in neonatal CD4(+) T cells. The Th2 phenotype of the IL-4(+)CD4(+) T cells could be reinforced in the presence of TGF-β. Although the IL-4(+)CD4(+) T cells most likely originate from CD31(+)CD4(+) T recent thymic emigrants, CD31 was downregulated prior to secretion of IL-4. Notably, the secretion of IL-4 requires a so far unidentified trigger in neonatal T cells. This emphasizes that cytokine expression and secretion are differentially regulated processes. Our data support the hypothesis of an endogenously poised cytokine profile in neonates and suggest a link between cytokine production and the developmental stage of an organism. The determination of the IL-4 isoform-expressing cells in humans might allow the identification of Th2 precursor cells, which could provide novel intervention strategies directed against Th2-driven immunopathologies such as allergies.
Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Katrin
K
Hebel
Division of Cardiology, Department of Internal Medicine, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Soenke
S
Weinert
Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany; and.
Benno
B
Kuropka
Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Julienne
J
Knolle
Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Bernhard
B
Kosak
Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Gerhard
G
Jorch
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Christoph
C
Arens
Leibniz-Institut für Molekulare Pharmakologie, 13125 Berlin, Germany; and.
Eberhard
E
Krause
Division of Cardiology, Department of Internal Medicine, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany;
Ruediger C
RC
Braun-Dullaeus
Department of Experimental Pediatrics, University Hospital, Otto-von-Guericke University, 39120 Magdeburg, Germany; Monika.Brunner-Weinzierl@med.ovgu.de.
Monika C
MC
Brunner-Weinzierl
D005260:Female; D050990:GATA3 Transcription Factor / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D015847:Interleukin-4 / Q000276:immunology*; D008297:Male; D020033:Protein Isoforms / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C508598:IL4 protein, human; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D015847:Interleukin-4