The potential role of iNKT cells in experimental allergic encephalitis and multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic inflammatory demyelination of the central nervous system (CNS). MS has been thought as Th1 (T helper) and Th17 cells mediated disease, but cells of the innate immune system play an important role both in the initiation and progression of MS. The invariant Natural Killer T (iNKT) cells are the unique innate lymphocytes subtype involved in inflammation and autoimmune disorders and secretes cytokines such as interferon gamma (IFN-γ), Interleukin (IL)-10, IL-4 and IL-13. A reduction in number or defect in function of iNKT cells has been associated with an increased prevalence of autoimmune disorders indicating that iNKT cells have an immune-regulatory role in autoimmune disorders. Also, the protective role of iNKT cells has been extensively studied in EAE and the results of these studies show that iNKT cells might be a target for therapeutic purposes, but needs more extensive studies of their biology. In this review, we will attempt to show the protective role of iNKT cells in the pathogenesis of EAE and human disease.     

Immune tolerance in multiple sclerosis

Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been identified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4(+) myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8(+) myelin-specific T cells.     

Therapeutic Effect of EDTA in Experimental Model of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic, neurodegenerative disease that causes central nervous system (CNS) demyelination and affects approximately 2 million people worldwide. The aim of the present study was to test the therapeutic effect of ethylene diamine tetra acetic acid (EDTA) in an experimental model of MS. The experiment was done on male C57BL/6 mice aged 6–8 weeks. The experimental autoimmune encephalomyelitis (EAE) was induced using 250 μg of the MOG35-55 peptide emulsified in CFA and injected subcutaneously on day 0 over two flank areas. In addition, 250?ng of pertussis toxin in 400 μl PBS was injected i.p. on days 0 and 2. In the treatment group, EDTA was administered i.p. at a dose 75?mg/kg/day. The mice were sacrificed 21 days after EAE induction and blood samples were taken from their hearts. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. Results: Our results showed that treatment with EDTA caused a significant delay in the time of onset and a significant reduction in severity of the EAE. Histological analysis indicated that there was not any plaque in the group of EDTA-treated mice whereas 5?±?1 plaques were detected in controls. The density of mononuclear infiltration in the CNS of EDTA-treated mice was lower than controls. In the group of EDTA-treated mice, using the FRAP test, total serum antioxidant power was high and significant in comparison to the controls. Moreover, the serum level of nitric oxide in the treatment group was significantly less than the control group, and, also, the levels of IFN-γ in the cell culture supernatant of treated mice splenocytes was lower than control group. These data indicate that EDTA therapy can effectively attenuate EAE progression.     

Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis

The therapeutic potency of M2000 (β-D-mannuronic acid), a novel designed nonsteroidal anti-inflammatory drug with immunosuppressive property in T-cell-mediated autoimmune disease, was tested. The influence of M2000 on myelin basic protein (MBP)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was assessed. M2000 at two doses, 40 and 80 mg/kg/day, was administered intraperitoneally (i.p.) to prevention and treatment groups, respectively. Onset of i.p. injections of M2000 to prophylactic and therapeutic groups was day-1 and day-7 postimmunization. The WEHI-164 cell line was used for assaying the tolerability against M2000. The results of this experiment showed that the treatment of EAE with M2000 could significantly suppress disease development both prophylactically and therapeutically; the onset and symptoms of EAE in Lewis rats could be suppressed following the administration of M2000. Clinical improvement was accompanied by a marked decrease in mean numbers of vessels with perivascular cellular infiltration in M2000-treated rats compared with nontreated control. Disease suppression was associated with a marked suppression of MBP-specific T-cell reactivity in vitro, without any evidence for a generalized impairment of T-cell activity. Moreover, M2000 also showed a very high tolerability compared with certain steroidal and nonsteroidal anti-inflammatory drugs. Collectively, our data suggest that M2000 may provide a novel therapeutic option for T-cell-mediated autoimmune diseases in animal models and possibly in humans.     

Therapeutic effects of dasatinib in mouse model of multiple sclerosis

Abstract

Background: Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. Dasatinib (Sprycel) is a selective protein tyrosine kinase inhibitor with immunomodulatory properties that abrogates multiple signal transduction pathways in immune cells. In the present research, our aim was to test the therapeutic efficacy of dasatinib in experimental model of MS.

Methods: We performed EAE induction in female C57BL/6 mice by myelin oligodendrocyte glycoprotein_35–55 (MOG_35–55) in Complete Freund’s Adjuvant (CFA) emulsion, and used dasatinib for the treatment of EAE. During the course of study, clinical evaluation was assessed, and on day 21 post-immunization blood samples were taken from the heart of mice for tumor necrosis factor-alpha (TNF-α), nitric oxide (NO) and antioxidants capacity evaluation. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Also for in vitro analysis, we used C6 astrocytoma cell line to evaluate the inhibitory effects of dasatinib in cell proliferation and matrix metalloproteinase-2 (MMP-2) activity.

Results: Our findings demonstrated that dasatinib had beneficial effects on EAE by lower incidence, attenuation in the severity and a delay in the onset of disease. The serum level of NO and TNF-α in dasatinib treated mice was significantly lower than control mice. In vitro, dasatinib inhibited cell proliferation and MMP-2 activity.

Conclusion: Dasatinib with its potential therapeutic effects and immunomodulatory properties may be recommended, after additional necessary tests and trials, for the treatment of MS.     

Artemisinin therapeutic efficacy in the experimental model of multiple sclerosis

Context: The immune system through T-helper 1 (Th1) and Th17 cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), whereas the Th2 responses inhibit myelin degeneration. Artemisinin, as an anti-malaria as its agent, has been used widely in the treatment of malaria, shifts the lymphocyte responses from Th1 to Th2.

Objective: In this study, we have investigated the therapeutic effects of artemisinin on the EAE treatment.

Materials and methods: EAE was induced in the inbred C57BL6 mice. High and low doses of prednisolone and artemisinin were injected daily with the control and test groups, respectively. The spleen and the brain of the mice were removed and used for ELISA and histological studies.

Results: The mean weight of mice was significantly (p value?p value p value?p value?Conclusions: Since, artemisinin can shift the immune responses from Th1 to Th2, therefore, it can be helpful in the treatment of MS after more investigation.     

Variable effects of cyclophosphamide in rodent models of experimental allergic encephalomyelitis

In this study, we have evaluated the effects of cyclophosphamide on the development of experimental allergic encephalomyelitis (EAE) in four EAE rodent models: monophasic EAE in Lewis rats, protracted relapsing (PR)‐EAE in DA rats, myelin oligodendrocyte protein (MOG)‐induced EAE in C57Bl/6 mice and proteolipid protein (PLP)‐induced EAE in Swiss/Jackson Laboratory (SJL) mice. Cyclophosphamide, administered either prophylactically or therapeutically, suppressed most strongly the clinical symptoms of PR‐EAE in DA rats. Treated rats in this group also exhibited the lowest degree of inflammatory infiltration of the spinal cord, as well as the lowest levels of nuclear factor kappa B, interleukin‐12 and interferon‐gamma. Cyclophosphamide prophylactically, but not therapeutically, also delayed significantly the onset of EAE in Lewis rats. In contrast, regardless of the treatment regimen used, was unable to influence the clinical course of EAE in either MOG‐induced EAE in C57Bl/6 mice or PLP‐induced EAE in SJL mice. This heterogeneous pharmacological response to cyclophosphamide suggests that significant immunopathogenic differences exist among these EAE rodent models that must be considered when designing preclinical studies. In addition, the effectiveness of cyclophosphamide in dark Agouti (DA) rats with PR‐EAE suggests that this may be a particularly useful model for studying novel therapeutic approaches for refractory and rapidly worsening multiple sclerosis in human patients.     

Immunomodulatory potential of acemannan (polysaccharide from Aloe vera) against radiation induced mortality in Swiss albino mice

Plant polysaccharides have been reported to stimulate growth, differentiation and proliferation of hematopoietic progenitor and stem cells to protect against the deleterious effects of radiations. This study evaluated the radioprotective potential of acemannan, a major polysaccharide component of aloe vera gel. Treatment of mice with 50?mg/kg body weight of acemannan by oral gavage for 7 days was able to protect against the radiation-induced mortality. Seven-day pretreatment or post-treatment of mice with acemannan resulted in the increase in median survival by 60 and 20%, respectively. The decrease in mortality can be attributed to the induction of hematopoiesis (peripheral lymphocytes counts, spleen cellularity, spleen index) and the upregulation of cytokines like TNF-α and IL-1 by acemannan in irradiated mice. Data indicate that acemannan has the ability to protect mice against radiation-induced mortality by immunomodulation and can be developed as a radiation damage mitigation agent.     

Therapeutic potential of carbon monoxide in multiple sclerosis

Carbon monoxide (CO) is produced during the catabolism of free haem, catalyzed by haem oxygenase (HO) enzymes, and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation and anti-proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The carbon monoxide-releasing molecules (CORMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems. This review covers the physiological and anti-inflammatory properties of the HO/CO pathway in the central nervous system. It also discusses the effects of CORMs in preclinical models of inflammation. The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease-modifying properties in multiple sclerosis.     

Immunomodulatory effects of Aloe vera and its fractions on response of macrophages against Candida albicans

Natural products are important resources in traditional medicine and have been long used for prevention and treatment of many diseases. Medicinal plants have immunomodulatory properties. Aloe is one of the herbal medicines widely used in natural treatment and alternative therapy for various types of diseases. Aloe vera has been shown to modulate the immune response. Macrophages have been shown to play an essential role as the first line of defense against invading pathogen. Candida albicans is a communal and opportunistic pathogen in humans. In this study, we investigated the effect of A. vera extract and its fractions on infected macrophages with C. albicans. Viability of intraperitoneal macrophages was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Cell viability of infected macrophages was increased by the extract and dose of some isolated fractions dependently. The extract as well as R100, R50, R30, and R10 fractions of A. vera significantly increased cell viability of macrophages in most doses. R5 and F5 fractions showed no significant difference in comparison with control group. Further studies in animal models and human are necessary to clarify the modulatory effects of A. vera on macrophage function. Isolation and purification of A. vera components are also needed to find out the effective molecules.     

Inflammasome activation in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE)

The aptly named inflammasomes are powerful signaling complexes that sense inflammatory signals under a myriad of conditions, including those from infections and endogenous sources. The inflammasomes promote inflammation by maturation and release of the pro‐inflammatory cytokines, IL‐1β and IL‐18. Several inflammasomes have been identified so far, but this review focuses mainly on the NLRP3 inflammasome. By still ill‐defined activation mechanisms, a sensor molecule, NLRP3 (NACHT, LRR and PYD domains‐containing protein 3), responds to danger signals and rapidly recruits ASC (apoptosis‐associated speck‐like protein containing a CARD) and pro‐caspase‐1 to form a large oligomeric signaling platform—the inflammasome. Involvement of the NLRP3 inflammasome in infections, metabolic disorders, autoinflammation, and autoimmunity, underscores its position as a central player in sensing microbial and damage signals and coordinating pro‐inflammatory immune responses. Indeed, evidence in patients with multiple sclerosis (MS) suggests inflammasome activation occurs during disease. Experiments with the mouse model of MS, experimental autoimmune encephalomyelitis (EAE), specifically describe the NLRP3 inflammasome as critical and necessary to disease development. This review discusses recent studies in EAE and MS which describe associations of inflammasome activation with promotion of T cell pathogenicity, infiltration of cells into the central nervous system (CNS) and direct neurodegeneration during EAE and MS.     

Characterization of the encephalitogenic immune response in a model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) can be actively induced with the extracellular domain of myelin oligodendrocyte glycoprotein (MOG 1-125). MOG-EAE closely mimics multiple sclerosis (MS) especially as far as demyelination, lesion formation and axonal pathology are concerned. MOG 91-108 is the encephalitogenic stretch within MOG 1-125 in two EAE-susceptible MHC congenic LEW rat strains [LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n))] and DA (RT1(av1)) rats. In LEW.1AV1 rats, disease could be induced with MOG 96-104 and to a lesser extent with MOG 98-106, whereas in LEW.1N rats, only MOG 98-106 was pathogenic. Both peptides bound well to their restricting MHC class II molecules, i.e., RT1.D(n) in the LEW.1N rat and RT1.B(a) in the LEW.1AV1 rat. TCR spectratyping of MOG 91-108 immunized LEW.1N, LEW.1AV1 and DA rats revealed that MHC class II determined the TCRBV preference of CNS infiltrating T cells. The data demonstrate that the most critical factor in inducing MS like pathology is presentation of autoantigenic peptides on MHC class II molecules resulting in demyelination and axonal pathology.     

CVSnet: A machine learning approach for automated central vein sign assessment in multiple sclerosis

The central vein sign (CVS) is an efficient imaging biomarker for multiple sclerosis (MS) diagnosis, but its application in clinical routine is limited by inter‐rater variability and the expenditure of time associated with manual assessment. We describe a deep learning‐based prototype for automated assessment of the CVS in white matter MS lesions using data from three different imaging centers. We retrospectively analyzed data from 3 T magnetic resonance images acquired on four scanners from two different vendors, including adults with MS (n = 42), MS mimics (n = 33, encompassing 12 distinct neurological diseases mimicking MS) and uncertain diagnosis (n = 5). Brain white matter lesions were manually segmented on FLAIR* images. Perivenular assessment was performed according to consensus guidelines and used as ground truth, yielding 539 CVS‐positive (CVS⁺) and 448 CVS‐negative (CVS^?) lesions. A 3D convolutional neural network (“CVSnet”) was designed and trained on 47 datasets, keeping 33 for testing. FLAIR* lesion patches of CVS⁺/CVS^? lesions were used for training and validation (n = 375/298) and for testing (n = 164/150). Performance was evaluated lesion‐wise and subject‐wise and compared with a state‐of‐the‐art vesselness filtering approach through McNemar's test. The proposed CVSnet approached human performance, with lesion‐wise median balanced accuracy of 81%, and subject‐wise balanced accuracy of 89% on the validation set, and 91% on the test set. The process of CVS assessment, in previously manually segmented lesions, was ~ 600‐fold faster using the proposed CVSnet compared with human visual assessment (test set: 4 seconds vs. 40 minutes). On the validation and test sets, the lesion‐wise performance outperformed the vesselness filter method (P < 0.001). The proposed deep learning prototype shows promising performance in differentiating MS from its mimics. Our approach was evaluated using data from different hospitals, enabling larger multicenter trials to evaluate the benefit of introducing the CVS marker into MS diagnostic criteria.     

Unaltered regulatory B-cell frequency and function in patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) typically characterized by the recruitment of T cells into the CNS. However, certain subsets of B cells have been shown to negatively regulate autoimmune diseases and some data support a prominent role for B cells in MS physiopathology. For B cells in MS patients we analyzed subset frequency, cytokine secretion ability and suppressive properties. No differences in the frequencies of the B-cell subsets or in their ability to secrete cytokines were observed between MS and healthy volunteers (HV). Prestimulated B cells from MS patients also inhibited CD4⁺CD25⁻ T cell proliferation with a similar efficiency as B cells from HV. Altogether, our data show that, in our MS patient cohort, regulatory B cells have conserved frequency and function.     

From classic to spontaneous and humanized models of multiple sclerosis: Impact on understanding pathogenesis and drug development

Multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), presents as a complex disease with variable clinical and pathological manifestations, involving different pathogenic pathways. Animal models, particularly experimental autoimmune encephalomyelitis (EAE), have been key to deciphering the pathophysiology of MS, although no single model can recapitulate the complexity and diversity of MS, or can, to date, integrate the diverse pathogenic pathways. Since the first EAE model was introduced decades ago, multiple classic (induced), spontaneous, and humanized EAE models have been developed, each recapitulating particular aspects of MS pathogenesis. The advances in technologies of genetic ablation and transgenesis in mice of C57BL/6J background and the development of myelin-oligodendrocyte glycoprotein (MOG)-induced EAE in C57BL/6J mice yielded several spontaneous and humanized EAE models, and resulted in a plethora of EAE models in which the role of specific genes or cell populations could be precisely interrogated, towards modeling specific pathways of MS pathogenesis/regulation in MS. Collectively, the numerous studies on the different EAE models contributed immensely to our basic understanding of cellular and molecular pathways in MS pathogenesis as well as to the development of therapeutic agents: several drugs available today as disease modifying treatments were developed from direct studies on EAE models, and many others were tested or validated in EAE. In this review, we discuss the contribution of major classic, spontaneous, and humanized EAE models to our understanding of MS pathophysiology and to insights leading to devising current and future therapies for this disease.     

Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10–60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re‐enforce tolerance of the autoaggressive T cells that drive tissue inflammation and injury. In this study, we have investigated whether the course of experimental autoimmune encephalomyelitis (EAE) in mice and marmosets can be altered by a potent tolerizing fusion protein. In addition, a multi‐parameter immunological analysis was performed in marmosets to assess whether the treatment induces modulation of EAE‐associated cellular and humoral immune reactions. The fusion protein, CTA1R9K‐hMOG10–60‐DD, contains a mutated cholera toxin A1 subunit (CTA1R9K), a dimer of the Ig binding D region of Staphylococcus aureus protein A (DD), and the human myelin oligodendrocyte glycoprotein (hMOG) sequence 10–60. We observed that intranasal application of CTA1R9K‐hMOG10–60‐DD seems to skew the immune response against myelin oligodendrocyte glycoprotein (MOG) towards a regulatory function. We show a reduced number of circulating macrophages, reduced MOG‐induced expansion of mononuclear cells in peripheral blood, reduced MOG‐induced production of interleukin (IL)‐17A in spleen, increased MOG‐induced production of IL‐4 and IL‐10 and an increased percentage of cells expressing programmed cell death‐1 (PD‐1) and CC chemokine receptor 4 (CCR4). Nevertheless, the treatment did not detectably change the EAE course and pathology. Thus, despite a detectable effect on relevant immune parameters, the fusion protein failed to influence the clinical and pathological outcome of disease. This result warrants further development and improvement of this specifically targeted tolerance inducing therapy.     

Kombucha tea ameliorates experimental autoimmune encephalomyelitis in mouse model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a mouse model for multiple sclerosis (MS), in which an inflammatory demyelination and axonal damage occurs. Kombucha tea is a fermented beverage made from kombucha mushroom, brewed tea, and sugar. In recent years kombucha tea has attracted interest due to its pharmacological properties like antioxidant effects. The aim of the present research was to test the therapeutic effect of kombucha tea in EAE. We induced EAE model in 18 female C57BL/6 mice by inoculation of myelin oligodendrocyte glycoprotein-35-55 (MOG_35-55) in complete Freund’s adjuvant emulsion. Then, in order to ameliorate EAE symptoms, we used kombucha tea. During the course of study clinical evaluation was assessed, and on the day 21 post-immunization, for evaluation of nitric oxide (NO), total antioxidants capacity and tumor necrosis factor-alpha (TNF-α), blood samples were taken from the heart of mice. The mice were sacrificed and brains and cerebellums of mice were removed for histological analysis. Our findings demonstrated that kombucha tea had beneficial effects on EAE by lower incidence, attenuation in the severity, and also a delay in the onset of disease. Histological analysis showed that inflammatory criteria including the number of infiltrated immune cells and plaques as well as demyelination in kombucha tea dosed mice were significantly lower than the control group. Also, in comparison with control mice, the serum levels of NO and TNF-α in kombucha tea-treated mice were significantly decreased. Kombucha tea with its potential therapeutic effects and immunomodulatory properties might be proposed, after additional necessary tests and trials, for treatment of MS.     

Enhanced TLR2 responses in multiple sclerosis

The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome‐derived Toll‐like receptor (TLR)2‐stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof‐of‐concept, we reported that decreasing systemic TLR2 responsiveness by administering very low‐dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll‐like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system‐targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing–remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS.     

Lack of adiponectin leads to increased lymphocyte activation and increased disease severity in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is a presumed autoimmune disease directed against central nervous system (CNS) myelin, in which diet and obesity are implicated as risk factors. Immune responses can be influenced by molecules produced by fat cells, called adipokines. Adiponectin is an adipokine with anti‐inflammatory effects. We tested the hypothesis that adiponectin has a protective role in the EAE model for MS, that can be induced by immunization with myelin antigens or transfer of myelin‐specific T lymphocytes. Adiponectin deficient (ADPKO) mice developed worse EAE with greater CNS inflammation, demyelination, and axon injury. Lymphocytes from myelin‐immunized ADPKO mice proliferated more, produced higher amounts of IFN‐γ, IL‐17, TNF‐α, IL‐6, and transferred more severe EAE than wild type (WT) lymphocytes. At EAE peak, the spleen and CNS of ADPKO had fewer regulatory T (Treg) cells than WT mice and during EAE recovery, Foxp3, IL‐10 and TGF‐β expression levels in the CNS were reduced in ADPKO compared with WT mice. Treatment with globular adiponectin in vivo ameliorated EAE, and was associated with an increase in Treg cells. These data indicate that adiponectin is an important regulator of T‐cell functions during EAE, suggesting a new avenue of investigation for MS treatment.