The key regulators of adult T helper cell responses, STAT6 and T-bet, are established in early life in mice

Authors

  • Shawn Rose,

    1. Department of Microbiology and Immunology, Miller School of Medicine at the University of Miami, Miami, FL, USA
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  • Patricia Guevara,

    1. Department of Microbiology and Immunology, Miller School of Medicine at the University of Miami, Miami, FL, USA
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  • Sandra Farach,

    1. Department of Microbiology and Immunology, Miller School of Medicine at the University of Miami, Miami, FL, USA
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  • Becky Adkins

    Corresponding author
    1. Department of Microbiology and Immunology, Miller School of Medicine at the University of Miami, Miami, FL, USA
    • Department of Microbiology and Immunology, R-138, 1600 NW 10th Ave., RMSB Room 3152A, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA, Fax: +1-305-243-4623
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Abstract

Murine neonatal immunity is typically Th2 biased. This is characterized by high-level IL-4 production at all phases of the immune response and poor IFN-γ memory responses. The differential expression of Th1/Th2 cytokines by neonates and adults could arise if the critical regulators of Th differentiation and function, STAT6 and T-bet, operate differently during the neonatal period. To test this idea, the Th cell responses of wild-type, T-bet-deficient, or STAT6-deficient mice were compared in vitro and in vivo. The absence of these factors had similar qualitative effects on the development of effector function in neonates and adults, i.e., if a Th lineage was inhibited or enhanced in adult animals, a similar phenomenon was observed in neonates. However, there was a striking difference observed in the in vivo Th1 memory responses of STAT6-deficient mice initially immunized as neonates. Antigen-specific IFN-γ production was increased 50–100-fold in STAT6-deficient neonates, achieving levels similar to those of STAT6-deficient adults. These findings demonstrate that STAT6 and T-bet signals are central in shaping Th responses in wild-type neonates, as in adult mice, and that the master regulators of Th cell development and function are already firmly established in early life.

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