Activation-Induced Cell Death and T Helper Subset Differentiation

  • Yufang Shi
  • Satish Devadas
  • Xiaoren Zhang
  • Liying Zhang
  • Achsah Keegan
  • Kristy Greeneltch
  • Jennifer Solomon
  • Zengrong Yuan
  • Erwei Sun
  • Catherine Liu
  • Jyoti Das
  • Megha Thayyil Satish
  • Lixin Wei
  • Jian-Nian Zhou
  • Arthur I. Roberts


Activation-induced cell death (AICD) has been demonstrated to occur in T cell hybridomas, immature thymocytes, and activated mature T cells. However, the molecular mechanisms and the physiological role of AICD in the differentiation of T helper cell subpopulations remain elusive. We have recently shown that activation-induced cell death in Thl and Th2 cells is executed via distinct mechanisms. Our results suggest that cytokine signals initiate the differentiation program, but it is the selective action of death effectors that determines the endpoint balance of differentiating T helper subsets. Activation-induced expression of TNF-related apoptosis-inducing ligand (TRAIL) is observed exclusively in Th2 clones and primary T helper cells differentiated under Th2 conditions, while the expression of CD95L (FasL) is mainly in Thl cells. Furthermore, Th2 cells are more resistant to either TRAIL- or CD95L-induced apoptosis than are Thl cells. Both Thl and Th2 cells can induce apoptosis in labeled Thl but not Th2 cells, and caspase inhibitor z-VAD inhibits AICD in Thl but not Th2 cells, implicating different mechanisms of AICD in these subpopulations. Blocking TRAIL CD95L significantly enhances IFN-g production in vitro. Likewise, young CD95-defective transgenic (MRL/MpJlpr/lpr) mice show a greater Thl response to ovalbumin immunization compared to control mice. Therefore, apoptosis mediated by CD95L and TRAIL is critical in determining the fate of differentiating T helper cells.


Immature Thymocyte Helper Subset Autoreactive Thymocyte Ovalbumin Immunization 
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© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Yufang Shi
  • Satish Devadas
  • Xiaoren Zhang
  • Liying Zhang
  • Achsah Keegan
  • Kristy Greeneltch
  • Jennifer Solomon
  • Zengrong Yuan
  • Erwei Sun
  • Catherine Liu
  • Jyoti Das
  • Megha Thayyil Satish
  • Lixin Wei
  • Jian-Nian Zhou
  • Arthur I. Roberts
    • 1
  1. 1.Department of Molecular Genetics, Microbiology and ImmunologyUniversity of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical SchoolPiscatawayUSA

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