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

Autor: Cunnusamy K; Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Baughman EJ; Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Franco J; Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Ortega SB; Department of Pathology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Sinha S; Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242, USA., Chaudhary P; Department of Neurology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Greenberg BM; Department of Neurology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Frohman EM; Department of Neurology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-9072, USA., Karandikar NJ; Department of Pathology, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242, USA. Electronic address: nitin-karandikar@uiowa.edu.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2014 May-Jun; Vol. 152 (1-2), pp. 115-26. Date of Electronic Publication: 2014 Mar 20.
DOI: 10.1016/j.clim.2014.03.005
Abstrakt: 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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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