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Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis.
J Immunol 2011; 187(2):1039-46JI

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by infiltration of pathogenic immune cells in the CNS resulting in destruction of the myelin sheath and surrounding axons. We and others have previously measured the frequency of human myelin-reactive T cells in peripheral blood. Using T cell cloning techniques, a modest increase in the frequency of myelin-reactive T cells in patients as compared with control subjects was observed. In this study, we investigated whether myelin oligodendrocyte glycoprotein (MOG)-specific T cells could be detected and their frequency was measured using DRB1*0401/MOG(97-109(107E-S)) tetramers in MS subjects and healthy controls expressing HLA class II DRB1*0401. We defined the optimal culture conditions for expansion of MOG-reactive T cells upon MOG peptide stimulation of PMBCs. MOG(97-109)-reactive CD4(+) T cells, isolated with DRB1*0401/MOG(97-109) tetramers, and after a short-term culture of PMBCs with MOG(97-109) peptides, were detected more frequently from patients with MS as compared with healthy controls. T cell clones from single cell cloning of DRB1*0401/MOG(97-109(107E-S)) tetramer(+) cells confirmed that these T cell clones were responsive to both the native and the substituted MOG peptide. These data indicate that autoantigen-specific T cells can be detected and enumerated from the blood of subjects using class II tetramers, and the frequency of MOG(97-109)-reactive T cells is greater in patients with MS as compared with healthy controls.

Authors+Show Affiliations

Department of Neurology, Yale School of Medicine, New Haven, CT 06510-8018, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21653833

Citation

Raddassi, Khadir, et al. "Increased Frequencies of Myelin Oligodendrocyte glycoprotein/MHC Class II-binding CD4 Cells in Patients With Multiple Sclerosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 187, no. 2, 2011, pp. 1039-46.
Raddassi K, Kent SC, Yang J, et al. Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis. J Immunol. 2011;187(2):1039-46.
Raddassi, K., Kent, S. C., Yang, J., Bourcier, K., Bradshaw, E. M., Seyfert-Margolis, V., ... Hafler, D. A. (2011). Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis. Journal of Immunology (Baltimore, Md. : 1950), 187(2), pp. 1039-46. doi:10.4049/jimmunol.1001543.
Raddassi K, et al. Increased Frequencies of Myelin Oligodendrocyte glycoprotein/MHC Class II-binding CD4 Cells in Patients With Multiple Sclerosis. J Immunol. 2011 Jul 15;187(2):1039-46. PubMed PMID: 21653833.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased frequencies of myelin oligodendrocyte glycoprotein/MHC class II-binding CD4 cells in patients with multiple sclerosis. AU - Raddassi,Khadir, AU - Kent,Sally C, AU - Yang,Junbao, AU - Bourcier,Kasia, AU - Bradshaw,Elizabeth M, AU - Seyfert-Margolis,Vicki, AU - Nepom,Gerald T, AU - Kwok,William W, AU - Hafler,David A, Y1 - 2011/06/08/ PY - 2011/6/10/entrez PY - 2011/6/10/pubmed PY - 2011/9/29/medline SP - 1039 EP - 46 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 187 IS - 2 N2 - Multiple sclerosis (MS) is an autoimmune disease characterized by infiltration of pathogenic immune cells in the CNS resulting in destruction of the myelin sheath and surrounding axons. We and others have previously measured the frequency of human myelin-reactive T cells in peripheral blood. Using T cell cloning techniques, a modest increase in the frequency of myelin-reactive T cells in patients as compared with control subjects was observed. In this study, we investigated whether myelin oligodendrocyte glycoprotein (MOG)-specific T cells could be detected and their frequency was measured using DRB1*0401/MOG(97-109(107E-S)) tetramers in MS subjects and healthy controls expressing HLA class II DRB1*0401. We defined the optimal culture conditions for expansion of MOG-reactive T cells upon MOG peptide stimulation of PMBCs. MOG(97-109)-reactive CD4(+) T cells, isolated with DRB1*0401/MOG(97-109) tetramers, and after a short-term culture of PMBCs with MOG(97-109) peptides, were detected more frequently from patients with MS as compared with healthy controls. T cell clones from single cell cloning of DRB1*0401/MOG(97-109(107E-S)) tetramer(+) cells confirmed that these T cell clones were responsive to both the native and the substituted MOG peptide. These data indicate that autoantigen-specific T cells can be detected and enumerated from the blood of subjects using class II tetramers, and the frequency of MOG(97-109)-reactive T cells is greater in patients with MS as compared with healthy controls. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/21653833/Increased_frequencies_of_myelin_oligodendrocyte_glycoprotein/MHC_class_II_binding_CD4_cells_in_patients_with_multiple_sclerosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21653833 DB - PRIME DP - Unbound Medicine ER -