Disease exacerbation of multiple sclerosis is characterized by loss of terminally differentiated autoregulatory CD8+ T cells

Disease exacerbation of multiple sclerosis is characterized by loss of terminally differentiated autoregulatory CD8+ T cells

Copyright © 2014 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 152(2014), 1-2 vom: 09. Mai, Seite 115-26
1. Verfasser: Cunnusamy, Khrishen (VerfasserIn)
Weitere Verfasser: Baughman, Ethan J, Franco, Jorge, Ortega, Sterling B, Sinha, Sushmita, Chaudhary, Parul, Greenberg, Benjamin M, Frohman, Elliot M, Karandikar, Nitin J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't CD8 IL-12 Multiple sclerosis Regulatory T cells Histocompatibility Antigens Class I Interleukin-2 Receptor alpha Subunit mehr... Tumor Necrosis Factor Receptor Superfamily, Member 7 Perforin 126465-35-8 Interleukin-12 187348-17-0 Interferon-gamma 82115-62-6 Leukocyte Common Antigens EC 3.1.3.48 Granzymes EC 3.4.21.-
Beschreibung
Zusammenfassung:Copyright © 2014 Elsevier Inc. All rights reserved.
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although its etiology remains unknown, pathogenic T cells are thought to underlie MS immune pathology. We recently showed that MS patients harbor CNS-specific CD8+ Tregs that are deficient during disease relapse. We now demonstrate that CNS-specific CD8+ Tregs were cytolytic and could eliminate pathogenic CD4+ T cells. These CD8+ Tregs were present primarily in terminally differentiated (CD27-, CD45RO-) subset and their suppression was IFNγ, perforin and granzyme B-dependent. Interestingly, MS patients with acute relapse displayed a significant loss in terminally differentiated CD8+ T cells, with a concurrent loss in expression of perforin and granzyme B. Pre-treatment of exacerbation-derived CD8+ T cells with IL-12 significantly restored suppressive capability of these cells through upregulation of granzyme B. Our studies uncover immune-suppressive mechanisms of CNS-specific CD8+ Tregs, and may contribute to design of novel immune therapies for MS
Beschreibung:Date Completed 02.07.2014
Date Revised 21.10.2021
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2014.03.005