Small interfering RNA-mediated gene silencing in T lymphocytes

J Immunol. 2002 Nov 15;169(10):5754-60. doi: 10.4049/jimmunol.169.10.5754.

Abstract

Introduction of small interfering RNAs (siRNAs) into a cell can cause a specific interference of gene expression known as RNA interference (RNAi). However, RNAi activity in lymphocytes and in normal primary mammalian cells has not been thoroughly demonstrated. In this report, we show that siRNAs complementary to CD4 and CD8alpha specifically reduce surface expression of these coreceptors and their respective mRNA in a thymoma cell line model. We show that RNAi activity is only caused by a subset of siRNAs complementary to the mRNA target and that ineffective siRNAs can compete with effective siRNAs. Using primary differentiated T lymphocytes, we provide the first evidence of siRNA-mediated RNAi gene silencing in normal nontransformed somatic mammalian lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4 Antigens / biosynthesis
  • CD4 Antigens / genetics
  • CD8 Antigens / biosynthesis
  • CD8 Antigens / genetics
  • Gene Silencing / immunology*
  • Green Fluorescent Proteins
  • Luminescent Proteins / biosynthesis
  • Luminescent Proteins / genetics
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • RNA Stability / immunology
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / chemistry*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Tumor Cells, Cultured

Substances

  • CD4 Antigens
  • CD8 Antigens
  • CD8alpha antigen
  • Luminescent Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Green Fluorescent Proteins