Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity

Hyun Hee Lee, Christine M. Hoeman, John C. Hardaway, F. Betul Guloglu, Jason S. Ellis, Renu Jain, Rohit Divekar, Danielle Tartar, Cara L. Haymaker, Habib Zaghouani

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Primary neonatal T cell responses comprise both T helper (Th) cell subsets, but Th1 cells express high levels of interleukin 13 receptor α1 (IL-13Rα1), which heterodimerizes with IL-4Rα. During secondary antigen challenge, Th2-produced IL-4 triggers the apoptosis of Th1 cells via IL-4Rα/IL-13Rα1, thus explaining the Th2 bias in neonates. We show that neonates acquire the ability to overcome the Th2 bias and generate Th1 responses starting 6 d after birth. This transition was caused by the developmental maturation of CD8α+CD4- dendritic cells (DCs), which were minimal in number during the first few days of birth and produced low levels of IL-12. This lack of IL-12 sustained the expression of IL-13Rα1 on Th1 cells. By day 6 after birth, however, a significant number of CD8α+CD4- DCs accumulated in the spleen and produced IL-12, which triggered the down-regulation of IL-13Rα1 expression on Th1 cells, thus protecting them against IL-4-driven apoptosis.

Original languageEnglish (US)
Pages (from-to)2269-2280
Number of pages12
JournalJournal of Experimental Medicine
Volume205
Issue number10
DOIs
StatePublished - Sep 29 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lee, H. H., Hoeman, C. M., Hardaway, J. C., Guloglu, F. B., Ellis, J. S., Jain, R., Divekar, R., Tartar, D., Haymaker, C. L., & Zaghouani, H. (2008). Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity. Journal of Experimental Medicine, 205(10), 2269-2280. https://doi.org/10.1084/jem.20071371