Immunologic Research

, Volume 28, Issue 3, pp 285–293

The role of activation-induced cell death in the differentiation of T-helper-cell subsets

Authors

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

DOI: 10.1385/IR:28:3:285

Cite this article as:
Roberts, A.I., Devadas, S., Zhang, X. et al. Immunol Res (2003) 28: 285. doi:10.1385/IR:28:3:285

Abstract

Activation-induced cell death (AICD) has been demonstrated in T-cell hybridomas, immature thymocytes, and activated mature T cells. However, the molecular mechanisms of AICD and its physiological role in T-helper-cell differentiation remain uncertain. Recently, we have shown that Th1 and Th2 cells have distinct mechanisms of AICD. Our findings suggest that signaling from cytokines initiates the differentiation program, but that the selective action of death effectors determines the fate of differentiating T-helper cells, and thus, the ultimate balance between T-helper subpopulations. Among T cells, activation-induced expression of the tumor necrosis factor (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 (Fas ligand) occurs mainly in Th1 cells. Furthermore, Th1 cells are more susceptible than Th2 cells to apoptosis induced through either TRAIL or CD95L, and radiolabeled Th1 cells can be induced into apoptosis via fratricide by both Th1 and Th2 cells, while Th2 cells are spared. The pan-caspase inhibitor, z-VAD, prevents AICD in Th1 cells, but not Th2 cells, indicating different mechanisms of AICD in each T-helper subtype. Antibody blockade of TRAIL and CD95L significantly boosts interferon-γ (IFN-γ) production in vitro. Also, young mice with mutant CD95 (MRL/MpJ-lpr/lpr) have a stronger Th1 response to ovalbumin immunization than do controls. We conclude that apoptosis mediated by CD95L and TRAIL is critical in the selective removal of differentiating T helper cells.

Key Words

ApoptosisAICDTRAILFasT Cell

Copyright information

© Humana Press Inc. 2003