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MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE.
Mult Scler. 2014 Sep; 20(10):1312-21.MS

Abstract

BACKGROUND

Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-like domain of myelin oligodendrocyte glycoprotein (MOG(Igd), residues 1-125) might induce distinct CD4+ T-cell response and/or a stronger CD8+ T-cell response, compared to the 21 amino acid immunodominant MHC II-associating peptide (p35-55).

OBJECTIVES

Compare both EAE and T-cell responses in C57BL/6 mice immunized with MOG(Igd) and MOG p35-55.

METHODS

Cytokine production, and chemokine receptor expression by CD4+ and CD8+ T cells in the mouse central nervous system (CNS), were analyzed by flow cytometry.

RESULTS

MOG(Igd) triggered progression to more severe EAE than MOG p35-55, despite similar time of onset and overall incidence. EAE in MOG(Igd)-immunized mice was characterized by an increased percentage of CXCR3+ interferon-γ-producing CD4+ T cells in CNS. The CD8+ T-cell response to both immunogens was similar.

CONCLUSIONS

Increased incidence of severe disease following MOG(Igd) immunization, accompanied by an increased percentage of CD4+ T cells in the CNS expressing CXCR3 and producing interferon-γ, identifies a pathogenic role for interferon-γ that is not seen when disease is induced with a single Major Histocompatibility Complex (MHC) II-associating epitope.

Authors+Show Affiliations

Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark towens@health.sdu.dk.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24552747

Citation

Mony, Jyothi T., et al. "MOG Extracellular Domain (p1-125) Triggers Elevated Frequency of CXCR3+ CD4+ Th1 Cells in the CNS of Mice and Induces Greater Incidence of Severe EAE." Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 20, no. 10, 2014, pp. 1312-21.
Mony JT, Khorooshi R, Owens T. MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE. Mult Scler. 2014;20(10):1312-21.
Mony, J. T., Khorooshi, R., & Owens, T. (2014). MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE. Multiple Sclerosis (Houndmills, Basingstoke, England), 20(10), 1312-21. https://doi.org/10.1177/1352458514524086
Mony JT, Khorooshi R, Owens T. MOG Extracellular Domain (p1-125) Triggers Elevated Frequency of CXCR3+ CD4+ Th1 Cells in the CNS of Mice and Induces Greater Incidence of Severe EAE. Mult Scler. 2014;20(10):1312-21. PubMed PMID: 24552747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE. AU - Mony,Jyothi T, AU - Khorooshi,Reza, AU - Owens,Trevor, Y1 - 2014/02/19/ PY - 2014/2/21/entrez PY - 2014/2/21/pubmed PY - 2015/10/28/medline KW - Central nervous system KW - T cells KW - chemokine receptors KW - cytokines KW - experimental autoimmune encephalomyelitis KW - immunogen KW - inflammation KW - interferon gamma KW - mouse study KW - myelin oligodendrocyte glycoprotein SP - 1312 EP - 21 JF - Multiple sclerosis (Houndmills, Basingstoke, England) JO - Mult Scler VL - 20 IS - 10 N2 - BACKGROUND: Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-like domain of myelin oligodendrocyte glycoprotein (MOG(Igd), residues 1-125) might induce distinct CD4+ T-cell response and/or a stronger CD8+ T-cell response, compared to the 21 amino acid immunodominant MHC II-associating peptide (p35-55). OBJECTIVES: Compare both EAE and T-cell responses in C57BL/6 mice immunized with MOG(Igd) and MOG p35-55. METHODS: Cytokine production, and chemokine receptor expression by CD4+ and CD8+ T cells in the mouse central nervous system (CNS), were analyzed by flow cytometry. RESULTS: MOG(Igd) triggered progression to more severe EAE than MOG p35-55, despite similar time of onset and overall incidence. EAE in MOG(Igd)-immunized mice was characterized by an increased percentage of CXCR3+ interferon-γ-producing CD4+ T cells in CNS. The CD8+ T-cell response to both immunogens was similar. CONCLUSIONS: Increased incidence of severe disease following MOG(Igd) immunization, accompanied by an increased percentage of CD4+ T cells in the CNS expressing CXCR3 and producing interferon-γ, identifies a pathogenic role for interferon-γ that is not seen when disease is induced with a single Major Histocompatibility Complex (MHC) II-associating epitope. SN - 1477-0970 UR - https://www.unboundmedicine.com/medline/citation/24552747/MOG_extracellular_domain__p1_125__triggers_elevated_frequency_of_CXCR3+_CD4+_Th1_cells_in_the_CNS_of_mice_and_induces_greater_incidence_of_severe_EAE_ L2 - https://journals.sagepub.com/doi/10.1177/1352458514524086?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -