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Updated: May 7, 2026

Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood
07:58

Quantitative Imaging of Lineage-specific Toll-like Receptor-mediated Signaling in Monocytes and Dendritic Cells from Small Samples of Human Blood

Published on: April 16, 2012

Increased mammalian target of rapamycin complex 2 signaling promotes age-related decline in CD4 T cell signaling and

Eric Perkey1, Diane Fingar, Richard A Miller

  • 1Department of Molecular, Cellular, and Developmental Biology, University of Michigan College of Literature, Science and the Arts, Ann Arbor, MI 48109;

Journal of Immunology (Baltimore, Md. : 1950)
|October 1, 2013
PubMed

Insights

Aging impairs CD4 T cell function by increasing TORC2 signaling. This study reveals that enhanced TORC2 activity, not TORC1, drives age-related T cell defects, offering a new therapeutic target.

Area of Science:

  • Immunology
  • Aging Research
  • Cellular Signaling

Background:

  • CD4 T cell function deteriorates with age.
  • Mammalian target of rapamycin (TOR) is linked to aging, but TORC1 and TORC2 roles in T cell aging are unclear.

Purpose of the Study:

  • To investigate the roles of TORC1 and TORC2 in age-related CD4 T cell functional decline.
  • To determine if increased TORC2 signaling contributes to aging-associated CD4 T cell defects.

Main Methods:

  • Analyzed TORC1 and TORC2 signaling in aged murine CD4 T cells.
  • Utilized Rheb overexpression for TORC1 activation and Rictor/Sin1 for TORC2 augmentation in young mouse CD4 T cells.
  • Assessed in vivo function of CD4 T cells with altered TOR signaling.

Main Results:

  • Aging increases TORC2 signaling in CD4 T cells, which rapamycin can block.
  • Augmented TORC2, but not TORC1, signaling in young CD4 T cells mimics aging-associated biochemical changes.
  • Elevated TORC2 signaling in young CD4 T cells causes in vivo functional impairments.

Conclusions:

  • Aging enhances TORC2 signaling in CD4 T cells.
  • Increased TORC2 activity is a key driver of age-related CD4 T cell dysfunction.
  • This suggests a novel model where heightened TORC2 signaling leads to T cell defects in aged mice.

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