Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation

被引:0
作者
Thomas Korn
Jayagopala Reddy
Wenda Gao
Estelle Bettelli
Amit Awasthi
Troels R Petersen
B Thomas Bäckström
Raymond A Sobel
Kai W Wucherpfennig
Terry B Strom
Mohamed Oukka
Vijay K Kuchroo
机构
[1] Center for Neurologic Diseases,Department of Pathology
[2] Brigham and Women's Hospital,Department of Cancer Immunology & AIDS
[3] Harvard Medical School,undefined
[4] Transplant Research Center,undefined
[5] Beth Israel Deaconess Medical Center,undefined
[6] Harvard Medical School,undefined
[7] Malaghan Institute of Medical Research,undefined
[8] P.O. Box 7060,undefined
[9] Laboratory Service,undefined
[10] Veterans Affairs Health Care System,undefined
[11] Stanford University School of Medicine,undefined
[12] Dana-Farber Cancer Institute,undefined
[13] Harvard Medical School,undefined
来源
Nature Medicine | 2007年 / 13卷
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摘要
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/IAb (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.
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页码:423 / 431
页数:8
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