CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis

Cell Mol Immunol. 2019 Jul;16(7):652-665. doi: 10.1038/s41423-018-0198-5. Epub 2019 Jan 11.


CD70 is the unique ligand of CD27 and is expressed on immune cells only upon activation. Therefore, engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70. However, the T cell-intrinsic effect and function of human CD70 remain underexplored. Herein, we describe that CD70 expression distinguishes proinflammatory CD4+ T lymphocytes that display an increased potential to migrate into the central nervous system (CNS). Upregulation of CD70 on CD4+ T lymphocytes is induced by TGF-β1 and TGF-β3, which promote a pathogenic phenotype. In addition, CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γ expression by both T helper subtypes. Moreover, adoptive transfer of CD70-/-CD4+ T lymphocytes induced less severe experimental autoimmune encephalomyelitis (EAE) disease than transfer of WT CD4+ T lymphocytes. CD70+CD4+ T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice, highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.

Keywords: CD27/CD70 pathway; CD70+CD4+ T lymphocytes; TCR1640 transgene mouse model; TGF-β1; TGF-β3; blood-brain barrier; endothelial cells; experimental autoimmune encephalitis; multiple sclerosis; soluble CD70.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD27 Ligand / metabolism*
  • Cells, Cultured
  • Central Nervous System / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Humans
  • Inflammation
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology*
  • Signal Transduction
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • CD27 Ligand
  • CD70 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7