Reciprocal expression of TRAIL and CD95L in Th1 and Th2 cells: Role of apoptosis in T helper subset differentiation

X. R. Zhang, L. Y. Zhang, S. Devadas, L. Li, A. D. Keegan, Y. F. Shi

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Upon activation, naïve T helper cells can differentiate into two major distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), as defined by their effector functions and cytokine secretion patterns. Cytokine milieu and costimulatory molecules have been shown to play an essential role in determining T helper differentiation. However, it is still unclear how the effects of signals of costimulatory molecules and cytokines are exerted during T helper differentiation. We show evidence suggesting that while cytokine signals initiate the differentiation program, the selective action of death effectors determines the end point balance of differentiating T helper subsets. We examined the expression of TNF-related apoptosis-inducing ligand (TRAIL) and CD95L in cloned and in vitro differentiated Th1 and Th2 cells. We found that activation-induced expression of TRAIL is exclusively observed in Th2 clones and primary T helper cells differentiated under the Th2 condition, while the expression of CD95L is mainly in Th1 cells. Furthermore, these two subsets exhibit distinct susceptibilities to TRAIL- and CD95L-mediated apoptosis. Th2 cells are more resistant to either TRAIL- or CD95L-induced apoptosis than Th1 cells. More importantly, both Th1 and Th2 cells could induce apoptosis in labeled Th1 but not Th2 cells. Blocking TRAIL and CD95L significantly enhance IFN-γ production in vitro. Likewise, young MRL/MpJ-lpr/lpr mice also showed more Th1 response to ovalbumin immunization as compared to MRL/MpJ+/+. Therefore, apoptosis mediated by CD95L and TRAIL is critical in determining the fate of differentiating T helper cells.

Original languageEnglish (US)
Pages (from-to)203-210
Number of pages8
JournalCell Death and Differentiation
Issue number2
StatePublished - Feb 1 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


  • Apoptosis
  • CD95 ligand
  • T helper cell type 1
  • T helper cell type 2


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