The mTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage Commitment

Greg M. Delgoffe, Thomas P. Kole, Yan Zheng, Paul E. Zarek, Krystal L. Matthews, Bo Xiao, Paul F. Worley, Sara C. Kozma, Jonathan D. Powell

Research output: Contribution to journalArticle

Abstract

Effector T cell differentiation requires the simultaneous integration of multiple, and sometimes opposing, cytokine signals. We demonstrated mTOR's role in dictating the outcome of T cell fate. mTOR-deficient T cells displayed normal activation and IL-2 production upon initial stimulation. However, such cells failed to differentiate into T helper 1 (Th1), Th2, or Th17 effector cells. The inability to differentiate was associated with decreased STAT transcription factor activation and failure to upregulate lineage-specific transcription factors. Under normally activating conditions, T cells lacking mTOR differentiated into Foxp3+ regulatory T cells. This was associated with hyperactive Smad3 activation in the absence of exogenous TGF-β. Surprisingly, T cells selectively deficient in TORC1 do not divert to a regulatory T cell pathway, implicating both TORC1 and TORC2 in preventing the generation of regulatory T cells. Overall, our studies suggest that mTOR kinase signaling regulates decisions between effector and regulatory T cell lineage commitment.

Original languageEnglish (US)
Pages (from-to)832-844
Number of pages13
JournalImmunity
Volume30
Issue number6
DOIs
StatePublished - Jun 19 2009

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Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Delgoffe, G. M., Kole, T. P., Zheng, Y., Zarek, P. E., Matthews, K. L., Xiao, B., Worley, P. F., Kozma, S. C., & Powell, J. D. (2009). The mTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage Commitment. Immunity, 30(6), 832-844. https://doi.org/10.1016/j.immuni.2009.04.014