title: Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation.
abstract: Treatment with ex vivo-generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)(35-55)/IA(b) (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. MOG tetramer-reactive, Foxp3(+) T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent the onset of disease. Foxp3(+) T cells isolated from the CNS were effective in suppressing naive MOG-specific T cells, but failed to control CNS-derived encephalitogenic T-eff that secreted interleukin (IL)-6 and tumor necrosis factor (TNF). Our data suggest that in order for CD4(+)Foxp3(+) T-reg to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.
authors: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors: Thomas
authors: T
authors: Korn
authors: Jayagopala
authors: J
authors: Reddy
authors: Wenda
authors: W
authors: Gao
authors: Estelle
authors: E
authors: Bettelli
authors: Amit
authors: A
authors: Awasthi
authors: Troels R
authors: TR
authors: Petersen
authors: B Thomas
authors: BT
authors: Bäckström
authors: Raymond A
authors: RA
authors: Sobel
authors: Kai W
authors: KW
authors: Wucherpfennig
authors: Terry B
authors: TB
authors: Strom
authors: Mohamed
authors: M
authors: Oukka
authors: Vijay K
authors: VK
authors: Kuchroo
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D018448:Models, Immunological; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D049452:Green Fluorescent Proteins