VIPER regulates naive T cell activation and effector responses: Implication in TLR4 associated acute stage T cell responses

Sci Rep. 2018 May 8;8(1):7118. doi: 10.1038/s41598-018-25549-8.


Naive T cells are known to express the modest level of TLR4 while it is known to go down during TCR activation. However, information towards the requirement of TLR4 signaling during TCR or mitogenic activation of naive wild-type T cells remains scanty. Here we have investigated the endogenous functional expression of TLR4 in naive mice T cells during TCR and mitogenic stimulation in presence of VIPER peptide (VP), an established inhibitor of TLR4 signaling. As expected we found that TLR4 expression goes down during TCR and mitogenic activation. Interestingly, we observed that VP treatment restores TLR4 expression on those activated T cells. Moreover, VP was found to regulate such activation of naive T cell as evident by reduction of CD25, CD69 expression, effector cytokines (IL-2, IFN-γ, TNF) production, T cell proliferation and down-regulation of T cell activation-dependent Fas (CD95), FasL (CD95L) expression. Together, our current observation highlights a possible requirement of TLR4 responses in T cells, which might have possible implication towards the pathogenic acute phase activation of naive T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Cytokines / drug effects
  • Cytokines / genetics
  • Fas Ligand Protein / genetics
  • Gene Expression Regulation / drug effects
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lectins, C-Type / genetics
  • Mice
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / genetics*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / drug effects
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Viral Proteins / chemistry
  • Viral Proteins / pharmacology*


  • A46R protein, vaccinia virus
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Cytokines
  • Fas Ligand Protein
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Proteins