Korn, T, Reddy, J, Gao, W, Bettelli, E, Awasthi, A, Petersen, TR et al.. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13: 423-431

Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature Medicine (Impact Factor: 27.36). 05/2007; 13(4):423-31. DOI: 10.1038/nm1564
Source: PubMed


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.

Download full-text


Available from: Terry B. Strom
  • Source
    • "Mice B10.PL mice, tg4 mice [18], C57BL/6 mice, FVB mice, Foxp3gfp.KI mice [19] and hCD2-DkTbRII mice [20] were bred and kept in the animal facility of the University Medical Centre Hamburg-Eppendorf under specific pathogen-free conditions . F1 mice were generated by mating of Foxp3gfp.KI mice with tg4 mice. "

    Full-text · Dataset · Apr 2015
  • Source
    • "As in other diseases, the Treg enrichment was insufficient to control the disease. This was attributed to production of the cytokines IL-6 and TNF at the site of inflammation (Korn et al., 2007); similar findings have also been reported for sarcoidosis (Torgerson, 2006). Our data, as well the findings reviewed above, suggest a general pattern in the dynamics of Treg cells during the peak phase of autoimmune inflammation: a counter-intuitive, localized enrichment of Treg occurring at the site of inflammation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently leads to the assumption that Treg presence in prevailing numbers is indicative of immunosuppression. We hypothesized that this assumption may be false. We examined models of three different diseases caused by organ-specific autoimmune responses: primary biliary cirrhosis, atherosclerosis and rheumatoid arthritis (RA). We examined indicators of relative abundance of Treg compared to pro-inflammatory T cells, during peak inflammation. In all cases, the results were compatible with a relative enrichment of Treg at the site of inflammation or its most proximal draining lymph node. Conversely, in healthy mice or mice successfully protected from disease via a Treg-mediated mechanism, the data did not suggest that any Treg accumulation was occurring. This counter-intuitive finding may appear to be at odds with the immunosuppressive nature of Treg. Yet extensive previous studies in RA show that an accumulation of Treg occurs at peak inflammation, albeit without resulting in suppression, as the Treg suppressive function is overcome by the cytokine-rich environment. We suggest that this is a ubiquitous feature of autoimmune inflammation. Treg abundance in patient samples is increasingly used as an indicator of a state of immunosuppression. We conclude that this strategy should be revisited as it may potentially be a source of misinterpretation. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.
    Full-text · Article · Feb 2015 · Immunobiology
  • Source
    • "Initially, Th1 lymphocytes were attributed as being primarily responsible for the demyelination of neurons [24] [25]. However Korn et al. showed that Th17 lymphocytes would be important both at the beginning and at the peak of the disease and possibly Treg lymphocytes at later stages [26]. Moreover, it has been reported that MOG (myelin oligodendrocyte glycoprotein) specific, highly pathogenic Th1 lymphocytes are necessary to allow Th17 entry into the CNS [27]; and it has been suggested that the proportion between Th1 and Th17 determines the site where inflammation occurs in the CNS [28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The Silences of the Archives, the Reknown of the Story. The Martin Guerre affair has been told many times since Jean de Coras and Guillaume Lesueur published their stories in 1561. It is in many ways a perfect intrigue with uncanny resemblance, persuasive deception and a surprizing end when the two Martin stood face to face, memory to memory, before captivated judges and a guilty feeling Bertrande de Rols. The historian wanted to go beyond the known story in order to discover the world of the heroes. This research led to disappointments and surprizes as documents were discovered concerning the environment of Artigat’s inhabitants and bearing directly on the main characters thanks to notarial contracts. Along the way, study of the works of Coras and Lesueur took a new direction. Coming back to the affair a quarter century later did not result in finding new documents (some are perhaps still buried in Spanish archives), but by going back over her tracks, the historian could only be struck by the silences of the archives that refuse to reveal their secrets and, at the same time, by the possible openings they suggest, by the intuition that almost invisible threads link here and there characters and events.
    Full-text · Article · Jan 2015 · Stem cell International
Show more