title: Apoptotic cell-treated dendritic cells induce immune tolerance by specifically inhibiting development of CD4⁺ effector memory T cells.
abstract: CD4(+) memory T cells play an important role in induction of autoimmunity and chronic inflammatory responses; however, regulatory mechanisms of CD4(+) memory T cell-mediated inflammatory responses are poorly understood. Here we show that apoptotic cell-treated dendritic cells inhibit development and differentiation of CD4(+) effector memory T cells in vitro and in vivo. Simultaneously, intravenous transfer of apoptotic T cell-induced tolerogenic dendritic cells can block development of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of the central nervous system in C57 BL/6J mouse. Our results imply that it is effector memory CD4(+) T cells, not central memory CD4(+) T cells, which play a major role in chronic inflammatory responses in mice with EAE. Intravenous transfer of tolerogenic dendritic cells induced by apoptotic T cells leads to immune tolerance by specifically blocking development of CD4(+) effector memory T cells compared with results of EAE control mice. These results reveal a new mechanism of apoptotic cell-treated dendritic cell-mediated immune tolerance in vivo.
authors.affiliation: Department of Neurology, Thomas Jefferson University, 901 Walnut Street, Philadelphia, PA, 19107, USA.|Laboratory of Liver Cancer Immunotherapy, Greenslopes Private Hospital, School of Medicine, University of Queensland, Greenslopes, Brisbane, QLD, 4120, Australia.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Thomas Jefferson University, 901 Walnut Street, Philadelphia, PA, 19107, USA. Guang-Xian.Zhang@jefferson.edu.
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Thomas Jefferson University, 901 Walnut Street, Philadelphia, PA, 19107, USA. a.m.rostami@jefferson.edu.
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D061166:Peripheral Tolerance
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)
keywords: Apoptosis; Autoimmunity; Dendritic cell; Immune tolerance; Immunotherapy; Inflammation; Memory T cell