CD70 defines a subset of proinflammatory and CNS-pathogenic T1/T17 lymphocytes and is overexpressed in multiple sclerosis.

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 T1 and T17 profile of lymphocytes and is important for T-bet and IFN-γ expression by both T helper subtypes. Moreover, adoptive transfer of CD70CD4 T lymphocytes induced less severe experimental autoimmune encephalomyelitis (EAE) disease than transfer of WT CD4 T lymphocytes. CD70CD4 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 T1/T17 lymphocytes infiltrating the CNS.