Developmental expression of IL-12Rβ2 on murine naive neonatal T cells counters the upregulation of IL-13Rα1 on primary Th1 cells and balances immunity in the newborn

J Immunol. 2013 Jun 15;190(12):6155-63. doi: 10.4049/jimmunol.1202207. Epub 2013 May 6.

Abstract

Upon exposure to Ag on the day of birth, neonatal mice mount balanced primary Th1 and Th2 responses, with the former displaying upregulated IL-13Rα1 expression. This chain associates with IL-4Rα to form a heteroreceptor (IL-4Rα/IL-13Rα1) that marks the Th1 cells for death by IL-4 produced by Th2 cells during rechallenge with Ag, hence the Th2 bias of murine neonatal immunity. The upregulation of IL-13Rα1 on neonatal Th1 cells was due to the paucity of IL-12 in the neonatal environment. In this study, we show that by day 8 after birth, naive splenic T cells are no longer susceptible to IL-13Rα1 upregulation even when exposed to Ag within the neonatal environment. Furthermore, during the 8-d lapse, the naive splenic T cells spontaneously and progressively upregulate the IL-12Rβ2 chain, perhaps due to colonization by commensals, which induce production of IL-12 by cells of the innate immune system such as dendritic cells. In fact, mature T cells from the thymus, a sterile environment not accessible to microbes, did not upregulate IL-12Rβ2 and were unable to counter IL-13Rα1 upregulation. Finally, the 8-d naive T cells were able to differentiate into Th1 cells even independently of IL-12 but required the cytokine to counter upregulation of IL-13Rα1. Thus, in neonatal mice, IL-12, which accumulates in the environment progressively, uses IL-12Rβ2 to counter IL-13Rα1 expression in addition to promoting Th1 differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Animals, Newborn
  • Apoptosis / immunology
  • Cell Differentiation / immunology*
  • Cytokines / biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-13 Receptor alpha1 Subunit / immunology*
  • Interleukin-13 Receptor alpha1 Subunit / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Receptors, Interleukin-12 / biosynthesis*
  • Receptors, Interleukin-12 / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Up-Regulation

Substances

  • Cytokines
  • Interleukin-13 Receptor alpha1 Subunit
  • Receptors, Interleukin-12