The human CMV-UL86 peptide 981–1003 shares a crossreactive T-cell epitope with the encephalitogenic MOG peptide 34–56, but lacks the capacity to induce EAE in rhesus monkeys

Brok, Herbert; Boven, Leonie A.; Meurs, Marjan van; Rosbo, Nicole Kerlero de; Paul, Alberta; Kap, Yolanda S.; Jagessar, Anwar; Hintzen, Rogier Q.; Keir, Geoff; Bajramović, Jeffrey J.; Ben‐Nun, Avraham; Bauer, Jan; Laman, Jon D.; Amor, Sandra; Hart, Bert A. ’t

doi:10.1016/j.jneuroim.2006.10.010

Cited by 51 publications

(50 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This type of T cells has been found in humans in the repertoire of effector memory T cells that keep chronic latent infection with CMV under control (Pietra et al, 2003). Interestingly, we also found that the MOG40-48 epitope shares high sequence similarity with a peptide encoded in the UL86 ORF of human CMV and that T cells raised against the CMV peptide crossreact with MOG34-56 (Brok et al, 2007). As marmosets are naturally infected with a human CMV-related β-herpesvirus, it is tempting to speculate that the effector memory T cells that cause MS-like disease in marmosets immunized with MOG34-56/IFA originate from the anti-CMV repertoire.…”

Section: Modeling the T Cell Response To Injurysupporting

confidence: 70%

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

et al. 2016

Self Cite

View full text Add to dashboard Cite

Abstract. The increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) in aging human populations creates a high unmet need for safe and effective medications. However, thus far the translation of pathogenic concepts developed in animal models into effective treatments for the patient has been notoriously difficult. The main reason is that currently used mouse-based animal models for the pipeline selection of promising new treatments were insufficiently predictive for clinical success. Regarding the high immunological similarity between human and non-human primates (NHPs), AIMID models in NHPs can help to bridge the translational gap between rodent and man. Here we will review the preclinical relevance of the experimental autoimmune encephalomyelitis (EAE) model in common marmosets (Callithrix jacchus), a small-bodied neotropical primate. EAE is a generic AIMID model projected on the human autoimmune neuro-inflammatory disease multiple sclerosis (MS).

show abstract

Section: Modeling the T Cell Response To Injurysupporting

confidence: 70%

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Numbers in the panels represent the time points (psd) when overt neurological signs were first observed. susceptible to EAE than marmosets (25). In the third monkey (M03027), EAE scores fluctuating between 0.5 and 1.0 were recorded from psd 50 onwards.…”

Section: Experiments Bmentioning

confidence: 95%

“…Three monkeys were withdrawn from their respective experiments without neurological impairment. One monkey (QK) had experienced serious body weight loss and was sacrificed preterm to avoid a sudden deterioration of the clinical state, as has been observed in rhesus monkeys in which immunization with MOG 34 -56 induced acute onset EAE (25). Two monkeys (Mi020 and Mi021) were sacrificed with mild signs of EAE (score 0.5) as they reached the end of the experiment.…”

Section: Statisticsmentioning

confidence: 99%

Fast Progression of Recombinant Human Myelin/Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis in Marmosets Is Associated with the Activation of MOG34–56-Specific Cytotoxic T Cells

Kap

Smith

Jagessar

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The recombinant human (rh) myelin/oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) model in the common marmoset is characterized by 100% disease incidence, a chronic disease course, and a variable time interval between immunization and neurological impairment. We investigated whether monkeys with fast and slow disease progression display different anti-MOG T or B cell responses and analyzed the underlying pathogenic mechanism(s). The results show that fast progressor monkeys display a significantly wider specificity diversification of anti-MOG T cells at necropsy than slow progressors, especially against MOG34–56 and MOG74–96. MOG34–56 emerged as a critical encephalitogenic peptide, inducing severe neurological disease and multiple lesions with inflammation, demyelination, and axonal injury in the CNS. Although EAE was not observed in MOG74–96-immunized monkeys, weak T cell responses against MOG34–56 and low grade CNS pathology were detected. When these cases received a booster immunization with MOG34–56 in IFA, full-blown EAE developed. MOG34–56-reactive T cells expressed CD3, CD4, or CD8 and CD56, but not CD16. Moreover, MOG34–56-specific T cell lines displayed specific cytotoxic activity against peptide-pulsed B cell lines. The phenotype and cytotoxic activity suggest that these cells are NK-CTL. These results support the concept that cytotoxic cells may play a role in the pathogenesis of multiple sclerosis.

show abstract

“…Clinical signs were scored daily by observers blinded to the treatment, using a previously described semiquantitative scale (27,31,32): 0 = no clinical signs; 0.5 = loss of appetite, vomiting; 1 = substantial reduction of general condition; 2 = ataxia, sensory loss, and/or visual problems; 2.5 = incomplete paralysis of one (hemiparesis) or both sides (paraparesis); 3 = complete paralysis of one (hemiplegia) or both sides (paraplegia); 4 = complete paralysis (quadriplegia); 5 = moribund. The rhMOG-induced EAE model in rhesus monkeys is characterized by acute onset and rapid disease progression, with the monkeys reaching a moribund state within 24 h. To avoid suffering, monkeys were euthanized at EAE score $ 2.5, or at score 2 when the animal was not expected to survive until the next day.…”

Section: Eae Induction and Monitoringmentioning

confidence: 99%

Antagonizing the α4β1 Integrin, but Not α4β7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

Haanstra

Hofman

Estêvão

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the α4 integrins expressed by T lymphocytes. The α4β1 integrin mediates migration of memory T lymphocytes into the CNS, whereas the α4β7 integrin mediates migration preferentially into gastrointestinal tissue. This paradigm was established primarily from investigations in rodents; thus, the objective of this investigation was to determine if blocking the α4β7 integrin exclusively would affect migration of T lymphocytes into the CNS of primates. The effects of the dual α4β1 and α4β7 antagonist natalizumab were compared with those of the α4β7 antagonist vedolizumab on experimental autoimmune encephalomyelitis in the rhesus monkey. Animals received an initial i.v. bolus of placebo, natalizumab (30 mg/kg), or vedolizumab (30 mg/kg) before intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein and then Ab once weekly thereafter. Natalizumab prevented CNS inflammation and demyelination significantly (p < 0.05), compared with time-matched placebo control animals, whereas vedolizumab did not inhibit these effects, despite saturating the α4β7 integrin in each animal for the duration of the investigation. These results demonstrate that blocking α4β7 exclusively does not inhibit immune surveillance of the CNS in primates.

show abstract

The human CMV-UL86 peptide 981–1003 shares a crossreactive T-cell epitope with the encephalitogenic MOG peptide 34–56, but lacks the capacity to induce EAE in rhesus monkeys

Cited by 51 publications

References 42 publications

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

Fast Progression of Recombinant Human Myelin/Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis in Marmosets Is Associated with the Activation of MOG34–56-Specific Cytotoxic T Cells

Antagonizing the α4β1 Integrin, but Not α4β7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

Contact Info

Product

Resources

About

The human CMV-UL86 peptide 981–1003 shares a crossreactive T-cell epitope with the encephalitogenic MOG peptide 34–56, but lacks the capacity to induce EAE in rhesus monkeys

Cited by 51 publications

References 42 publications

The common marmoset (&lt;i&gt;Callithrix jacchus&lt;/i&gt;): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

The common marmoset (&lt;i&gt;Callithrix jacchus&lt;/i&gt;): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

Fast Progression of Recombinant Human Myelin/Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis in Marmosets Is Associated with the Activation of MOG34–56-Specific Cytotoxic T Cells

Antagonizing the α4β1 Integrin, but Not α4β7, Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

Contact Info

Product

Resources

About

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain

The common marmoset (<i>Callithrix jacchus</i>): a relevant preclinical model of human (auto)immune-mediated inflammatory disease of the brain