Regenerating Immunotolerance in Multiple Sclerosis with Autologous Hematopoietic Stem Cell Transplant
Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system where evidence implicates an aberrant adaptive immune response in the accrual of neurological disability. The inflammatory phase of the disease responds to immunomodulation to varying degrees of efficacy; however, no t...
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Published in | Frontiers in immunology Vol. 9; p. 410 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
12.03.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system where evidence implicates an aberrant adaptive immune response in the accrual of neurological disability. The inflammatory phase of the disease responds to immunomodulation to varying degrees of efficacy; however, no therapy has been proven to arrest progression of disability. Recently, more intensive therapies, including immunoablation with autologous hematopoietic stem cell transplantation (AHSCT), have been offered as a treatment option to retard inflammatory disease, prior to patients becoming irreversibly disabled. Empirical clinical observations support the notion that the immune reconstitution (IR) that occurs following AHSCT is associated with a sustained therapeutic benefit; however, neither the pathogenesis of MS nor the mechanism by which AHSCT results in a therapeutic benefit has been clearly delineated. Although the antigenic target of the aberrant immune response in MS is not defined, accumulated data suggest that IR following AHSCT results in an immunotolerant state through deletion of pathogenic clones by a combination of direct ablation and induction of a lymphopenic state driving replicative senescence and clonal attrition. Restoration of immunoregulation is evidenced by changes in regulatory T cell populations following AHSCT and normalization of genetic signatures of immune homeostasis. Furthermore, some evidence exists that AHSCT may induce a rebooting of thymic function and regeneration of a diversified naïve T cell repertoire equipped to appropriately modulate the immune system in response to future antigenic challenge. In this review, we discuss the immunological mechanisms of IR therapies, focusing on AHSCT, as a means of recalibrating the dysfunctional immune response observed in MS. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Specialty section: This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology Reviewed by: Sergio Querol, Banc de Sang i Teixits, Spain; Michael Uhlin, Karolinska Institutet (KI), Sweden Edited by: Maria Carolina Oliveira, University of São Paulo, Brazil |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2018.00410 |