Journal of Biomedical Science

, Volume 5, Issue 4, pp 297–304 | Cite as

Atypical signaling defects prevent IL-2 gene expression inIpr/Ipr CD4-CD8-cells

  • Hong-Erh Liang
  • Yi-Ping Hsueh
  • Chia-Cheng Wu
  • Shu-Ching Hsu
  • Shou-Hwa Han
  • Ming-Zong Lai
Original Paper
Received:
Accepted:
  • 25 Downloads

Abstract

T cells with CD4-CD8- (double negative, DN) phenotype in MRL-lpr/lpr mouse serve as a model to establish the correlation between the extremely low IL-2 gene expression and the specific signaling inactivation. The extent of non-responsiveness inlpr DN cells was distinctive in several unusual defects. First, the poor IL-2 production inlpr DN cells could not be restored by supplement of signals known to augment IL-2 response in normal T cells. Second, the activations of both mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) were attenuated inlpr DN cells upon direct activation by TPA/A23187. Third, IL-2 mRNA was degraded much faster inlpr DN cells than that in normal T cells. Fourth, of the four major transcriptional elements on IL-2 promoter, only AP-1 and nuclear factor of activated T cells (NFAT)-binding activities were suppressed inlpr DN T cells. Altogether, these results suggest that an extremely low level of IL-2 production inlpr DN T cells was due to both the increased instability of mRNA and the reduced activation of IL-2 gene promoter, the latter defect could be attributed to the inactivation of AP-1 and NF-AT as well as the poor activation of the upstream MAP kinase and JNK.

Key Words

Fas lpr/lpr SLE IL-2 gene expression JNK MAP kinase Signaling defect 
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Copyright information

© National Science Council 1998

Authors and Affiliations

  • Hong-Erh Liang
    • 4
    • 1
    • 2
  • Yi-Ping Hsueh
    • 4
    • 1
  • Chia-Cheng Wu
    • 4
    • 3
  • Shu-Ching Hsu
    • 4
    • 2
  • Shou-Hwa Han
    • 1
  • Ming-Zong Lai
    • 4
    • 1
    • 2
    • 3
  1. 1.Graduate Institute of Microbiology and ImmunologyNational Yang-Ming UniversityTaiwan/ROC
  2. 2.Graduate Institute of MicrobiologyNational Taiwan University, School of MedicineTaipeiTaiwan/ROC
  3. 3.Graduate Institute of ImmunologyNational Taiwan University, School of MedicineTaipeiTaiwan/ROC
  4. 4.Institute of Molecular BiologyAcademia Sinica NankangTaipeiTaiwan/ROC

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