Skip to main content

HTLV-1 Tax induces Th1 master regulator T-bet and thus IFN-γ in CD4+CCR4+ T-cells of virus-associated myelopathy patients

The plasticity inherent to the CD4+ T cell differentiation program especially as it pertains to regulatory T (Treg) cells has been implicated in the pathogeneses of multiple inflammatory diseases. Human T-lymphotropic virus type 1 (HTLV-1) is thought to effect transcriptional changes in infected T cells via HTLV-1 Tax that can cause once suppressive CD4+CD25+CCR4+ Treg cells to lose FOXP3 expression and produce IFN-γ. We hypothesized that spawning of such inflammatory Th1-like cells from infected CCR4+ T cells plays a key role in the pathogenesis of the neurodegenerative inflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this study, we demonstrated that Tax in cooperation with specificity protein 1 (Sp1) boosts the expression of the Th1 master regulator T box transcription factor (T-bet/Tbx21) and consequently IFN-γ. We established the presence of abundant CD4+CCR4+ T cells co-expressing the Th1 marker CXCR3 and producing T-bet/Tbx21 and IFN-γ in the CSF and spinal cord lesions of HAM/TSP patients. Finally, we tested treatments on ex vivo cell cultures from patients and found evidence that a therapy targeting CCR4+ T cells via antibody-dependent cellular cytotoxicity may represent a viable treatment option for HAM/TSP.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yoshihisa Yamano.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Araya, N., Sato, T., Tomaru, U. et al. HTLV-1 Tax induces Th1 master regulator T-bet and thus IFN-γ in CD4+CCR4+ T-cells of virus-associated myelopathy patients. Retrovirology 12, P44 (2015). https://doi.org/10.1186/1742-4690-12-S1-P44

Download citation

Keywords

  • Treg Cell
  • FOXP3 Expression
  • Spinal Cord Lesion
  • Cellular Cytotoxicity
  • Spastic Paraparesis