Cutting Edge: Th1 Cells Facilitate the Entry of Th17 Cells to the Central Nervous System during Experimental Autoimmune Encephalomyelitis

O’Connor, Richard A.; Prendergast, Catriona T.; Sabatos, Catherine A.; Lau, Clement; Leech, Melanie D.; Wraith, David C.; Anderton, Stephen M.

doi:10.4049/jimmunol.181.6.3750

Cited by 298 publications

(305 citation statements)

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“…Although both Th1 and Th17 cells could contribute to EAE pathogenicity, it appears that the ratio between the two subsets of T cells determines the severity of EAE in that predominance of Th17 over Th1 cells exacerbates inflammation and infiltration into the CNS (Bettelli et al, 2007;Stromnes et al, 2008). Furthermore, it has been proposed that Th1 cells enter non-inflamed CNS tissues prior to Th17 cells and initiate inflammation and that they facilitate the entry of Th17 cells (O'Connor et al, 2008). We have observed that ACA 83-95 induced a relatively lesser proportion of Th1 cells when compared with PLP 139151 (16.40 vs. 22.27%) and this difference in the generation of Th1 cells might have contributed to the less severe nature of EAE induced with ACA 83-95.…”

Section: Discussionmentioning

confidence: 99%

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

Massilamany

Steffen

Reddy

2010

Journal of Neuroimmunology

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Epitope from Acanthamoeba castellanii That Cross-React with Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis in SJL Mice" (2010). Jay Reddy Publications. 17. https://digitalcommons.unl.edu/vbsjayreddy/17 tein databases. This search resulted in the identification of one novel peptide spanning aa 83-95 of rhodanese-related sulfurtransferase in Acanthamoeba castellanii (ACA) and it induces EAE similar to that of PLP 139-151. Materials and methods MiceFour to six-week-old female SJL/J (H-2 s ) mice were obtained from the Jackson Laboratory (Bar Harbor, Maine). The mice were maintained in accordance with the animal protocol guidelines of the University of Nebraska-Lincoln, Lincoln, Nebraska. Peptide synthesis and immunization proceduresPLP 139-151 (HSLGKWLGHPDKF), ACA 83-95 (YFLLKWLGH-PNVS) and neuraminidase (NASE) 101-120 (EALVRQGLAKVAY-VYKPNNT) were synthesized on 9-fluorenylmethyloxycarbonyl chemistry (Neopeptide, Cambridge, Massachusetts). All peptides were HPLC-purified (N90%) and confirmed by mass spectroscopy. To measure recall responses 100 µg of each peptide emulsified in CFA was administered subcutaneously in the flank. For disease induction, Mycobacterium tuberculosis (MTB) H37RA extract (Difco Laboratories, Detroit, Michigan) was added as an additional component to a final concentration of 5 mg/ml. Pertussis toxin (List Biological Laboratories, Campbell, California) was administered (100 ng per mouse) intraperitoneally on day 0 and day 2 postimmunization. Identification of microbial peptides that mimic PLP 139-151PLP 139-151 is an immunodominant epitope in which the critical residues required for major histocompatibility complex (MHC) class II and T cell receptor (TCR)-binding have been well-characterized (Figure 1). By using PLP 139-151 as a putative antigen, we performed pattern search using the prosite scan of the Bioinformatics Toolkit

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Section: Discussionmentioning

confidence: 99%

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

Massilamany

Steffen

Reddy

2010

Journal of Neuroimmunology

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“…Studies of two different CCR6 À/À mouse strains (those from Dong's group [25] and our own) showed that these mice develop disease with CS similar to [25] or higher than those of WT controls. O'Connor et al [26] nonetheless established that in the absence of IFN-g 1 cells, Th17 cells do not induce EAE. Using Th1 and Th17 cells and avoiding cross-contamination between the polarized cell populations, these authors show that only Th1 cells have access to the non-inflamed CNS.…”

Section: Discussionmentioning

confidence: 99%

CCR6 regulates EAE pathogenesis by controlling regulatory CD4⁺ T‐cell recruitment to target tissues

et al. 2009

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The T-cell subsets, characterized by their cytokine production profiles and immune regulatory functions, depend on correct in vivo location to interact with accessory or target cells for effective immune responses. Differentiation of naive CD4 1 T cells into effectors is accompanied by sequentially regulated expression of the chemokine receptors responsible for cell recruitment to specific tissues. We studied CCR6 function in EAE, a CD4 1 T-cell-mediated CNS disease characterized by mononuclear infiltration and demyelination. CCR6 À/À mice showed an altered time course of EAE development, with delayed onset, a higher clinical score, and more persistent symptoms than in controls. An imbalanced cytokine profile and reduced Foxp3 1 cell frequency characterized CNS tissues from CCR6 À/À compared with CCR6 1/1 mice during the disease effector phase. Transfer of CCR6 1/1 Treg to CCR6 À/À mice the day before EAE induction reduced the clinical score associated with an increased in infiltrating Foxp3 1 cells and recovery of the cytokine balance in CCR6 À/À mouse CNS. Competitive assays between CCR6 1/1 and CCR6 À/À Treg adoptively transferred to CCR6 À/À mice showed impaired ability of CCR6 À/À Treg to infiltrate CNS tissues in EAE-affected mice. Our data indicate a CCR6 requirement by CD4 1 Treg to downregulate the CNS inflammatory process and neurological signs associated with EAE.Key words: Chemokines . EAE/MS . Inflammation . T cells Introduction EAE is a CNS disease characterized by mononuclear cell infiltration and demyelination; it is used to study certain aspects of human MS. EAE can be induced via immunization with neural antigens such as myelin oligodendrocyte glycoprotein (MOG). The immunopathological event in EAE and MS initiates when autoreactive T cells in the systemic immune compartment are activated and cross the blood-brain barrier [1]. Re-encounter of encephalitogenic T cells with their antigen leads to reactivation and expansion of autoreactive T cells, which in turn stimulate microglia/astrocyte activity, with increased release of proinflammatory cytokines and chemokines. The action of these mediators leads to demyelination and axon degeneration [2,3]. After antigen contact, naive CD4 1 T cells differentiate into various effector-cell subsets characterized by the cytokines they produce and by their immune regulatory functions. Th1 and Th17 cytokine profile effector cells and antigen-specific Treg have a critical role in EAE pathogenesis [4][5][6][7][8][9][10]. In MOG-induced EAE, both antigen-specific T-effector and Treg differentiate and proliferate in the periphery before migrating to the CNS [9]. Differentiation is accompanied by sequential expression of selectins, integrins, and chemokine receptors responsible for T-cell-subset recruitment to and extravasation at inflammation sites. The correct in vivo location of these cell subsets, necessary for their interaction with accessory or target cells, is regulated by [11], which are assumed to have a critical impact on MS and EAE pathogenesis [12]. St...

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“…In EAE Th17 cells are particularly important for the induction of the disease [48] and these cells enter the CNS after Th1 cells [51]. However the importance of Th17 cells in mouse models of autoimmune neuroinflammation is controversial [52].…”

Section: Tlrs In Multiple Sclerosismentioning

confidence: 99%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

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Cutting Edge: Th1 Cells Facilitate the Entry of Th17 Cells to the Central Nervous System during Experimental Autoimmune Encephalomyelitis

Cited by 298 publications

References 16 publications

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

CCR6 regulates EAE pathogenesis by controlling regulatory CD4⁺ T‐cell recruitment to target tissues

Evaluating the role of Toll-like receptors in diseases of the central nervous system

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Cutting Edge: Th1 Cells Facilitate the Entry of Th17 Cells to the Central Nervous System during Experimental Autoimmune Encephalomyelitis

Cited by 298 publications

References 16 publications

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

CCR6 regulates EAE pathogenesis by controlling regulatory CD4+ T‐cell recruitment to target tissues

Evaluating the role of Toll-like receptors in diseases of the central nervous system

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CCR6 regulates EAE pathogenesis by controlling regulatory CD4⁺ T‐cell recruitment to target tissues