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

Hyun-Hee Lee , 1 Christine M. Hoeman , 1 John C. Hardaway , 1 F. Betul Guloglu , 1 Jason S. Ellis , 1 Renu Jain , 1 Rohit Divekar , 1 Danielle M. Tartar , 1 Cara L. Haymaker , 1 and Habib Zaghouani 1,2

Primary neonatal T cell responses comprise both T helper (Th) cell subsets, but Th1 cells express high levels of interleukin 13 receptor  1 (IL-13R  1), which heterodimerizes with IL-4R  . During secondary antigen challenge, Th2-produced IL-4 triggers the apoptosis of Th1 cells via IL-4R  /IL-13R  1, 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 CD8  + CD4  dendritic cells (DCs), which were minimal in number during the fi rst few days of birth and produced low levels of IL-12. This lack of IL-12 sustained the expression of IL-13R  1 on Th1 cells. By day 6 after birth, however, a signifi cant number of CD8  + CD4  DCs accumulated in the spleen and produced IL-12, which triggered the down-regulation of IL-13R  1 expression on Th1 cells, thus protecting them against IL-4 – driven apoptosis.

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