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...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-γexpression 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.展开更多
基金T.D.holds a fellowship from the Fonds de Recherche du Québec-Santé(FRQS).L.T.holds scholarships from Universitéde Montréal and CRCHUM.E.P.holds a fellowship from the Multiple Sclerosis Society of Canada(MSSC)and the FRQS.S.Z.is supported by a fellowship from Biogen Canada.C.L.is supported by FRQS.A.P.holds the T1(senior)Canada Research Chair in Multiple Sclerosis.This work was funded by operating grants from the Canadian Institutes of Health Research(MOP 89885,PJI-153195)and from the MSSC(EGID 2382).We thank Jannie Borst for providing us with the CD70−/−mice.We thank Hartmut Wekerle for providing us with the TCR1640 mice.Special thanks to Magdalena Paterka and Volker Siffrin for providing the protocol for CD4+adoptive T cell transfer in RAG null mice.We would also like to thank the imaging platform,the pathology platform,and the flow cytometry platform from the CRCHUM for the excellent technical support and Alice M Roy and Elvia Gonzalez for their excellent technical animal support.
文摘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-γexpression 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.
