Effect of Trichostatin A on CD4 surface density in peripheral blood T cells

Folia Histochem Cytobiol. 2006;44(4):259-62.

Abstract

Acetylation level of chromatin histones is maintained by histone acetylases (HATs) and deacetylases (HDACs) and correlates with transcriptional activity of genes. Trichostatin A (TSA) is HDAC inhibitor that causes various effects in cells, including immunomodulation. The CD4 antigen is a key coreceptor involved in activation of T helper cells. Using quantitative real-time PCR (RQ-PCR) and flow cytometry techniques, we estimated CD4 transcript level and density of CD4 antigen on the surface of TSA-treated stimulated and unstimulated peripheral T cells. We observed a dose dependent decrease in CD4 mRNA level and antigen density on surface of TSA-treated stimulated T cells. However, we did not observe any significant TSA effect on CD4 mRNA and protein expression in unstimulated T cells. Our data suggest that TSA may induce biosynthesis of factors responsible for negative regulation of CD4 antigen expression in stimulated T cells. Our investigation may support previous observation that this drug has immunosuppresive effect on primary T cells and may be useful in treatment of certain autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / metabolism
  • CD4 Antigens / biosynthesis*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Chromatin / metabolism
  • Down-Regulation / drug effects*
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Hydroxamic Acids / therapeutic use
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects*

Substances

  • CD4 Antigens
  • Chromatin
  • Histones
  • Hydroxamic Acids
  • Immunosuppressive Agents
  • trichostatin A
  • Histone Deacetylases