The key regulators of adult T helper cell responses, STAT6 and T-bet, are established in early life in mice.
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-gamma 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-gamma 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.
Department of Microbiology and Immunology, Miller School of Medicine at the University of Miami, Miami, FL 33136, USA.
Shawn
S
Rose
Patricia
P
Guevara
Sandra
S
Farach
Becky
B
Adkins
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D050990:GATA3 Transcription Factor / Q000502:physiology; D007156:Immunologic Memory; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D050800:STAT6 Transcription Factor / Q000502:physiology*; D020825:T-Box Domain Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014157:Transcription Factors / Q000502:physiology*; D000098815:T-bet Transcription Factor
D050990:GATA3 Transcription Factor; D050800:STAT6 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D015847:Interleukin-4