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CD70 defines a subset of proinflammatory and CNS-pathogenic T
- Source :
- Cell Mol Immunol
- Publication Year :
- 2018
-
Abstract
- 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 T(H)1 and T(H)17 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 T(H)1/T(H)17 lymphocytes infiltrating the CNS.
- Subjects :
- Central Nervous System
Inflammation
Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
Th1 Cells
Lymphocyte Activation
Adoptive Transfer
Article
Tumor Necrosis Factor Receptor Superfamily, Member 7
Mice, Inbred C57BL
Mice
Animals
Humans
Th17 Cells
Cells, Cultured
CD27 Ligand
Signal Transduction
Subjects
Details
- ISSN :
- 20420226
- Volume :
- 16
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cellularmolecular immunology
- Accession number :
- edsair.pmid..........c12f2497b65118b3d1a080d4f7cc6151