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Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion

Citation

Chung, JY and Figgett, W and Fairfax, KA and Bernard, C and Chan, J and Toh, BH and Mackay, F and Alderuccio, F, Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion, Journal of Immunology, 192, (6) pp. 2593-2601. ISSN 0022-1767 (2014) [Refereed Article]

Copyright Statement

Copyright 2014 The American Association of Immunologists, Inc.

DOI: doi:10.4049/jimmunol.1203563

Abstract

The various mechanisms that have been described for immune tolerance govern our ability to control self-reactivity and minimize autoimmunity. However, the capacity to genetically manipulate the immune system provides a powerful avenue to supplement this natural tolerance in an Ag-specific manner. We have previously shown in the mouse model of experimental autoimmune encephalomyelitis that transfer of bone marrow (BM) transduced with retrovirus encoding myelin oligodendrocyte glycoprotein (MOG) promotes disease resistance and CD4(+) T cell deletion within the thymus. However, the consequence of this strategy on B cell tolerance is not known. Using BM from IgHMOG mice that develop MOG-specific B cell receptors, we generated mixed chimeras together with BM-encoding MOG. In these animals, the development of MOG-specific B cells was abrogated, resulting in a lack of MOG-specific B cells in all B cell compartments examined. This finding adds a further dimension to our understanding of the mechanisms of tolerance that are associated with this gene therapy approach to treating autoimmunity and may have important implications for Ab-mediated autoimmune disorders.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Development, Proliferation and Death
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
ID Code:134806
Year Published:2014
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-09-05
Last Modified:2019-10-18
Downloads:0

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