NDLI: Functional tolerance of CD8+ T cells induced by muscle-specific antigen expression.

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Functional tolerance of CD8+ T cells induced by muscle-specific antigen expression.

Content Provider	Semantic Scholar
Author	Calbo, Sébastien Delagrèverie, Héloïse M. Arnoult, Christophe Authier, F. J. Tron, François Boyer, Olivier
Copyright Year	2008
Abstract	Skeletal muscles account for more than 30% of the human body, yet mechanisms of immunological tolerance to this tissue remain mainly unexplored. To investigate the mechanisms of tolerance to muscle-specific proteins, we generated transgenic mice expressing the neo-autoantigen OVA exclusively in skeletal muscle (SM-OVA mice). SM-OVA mice were bred with OT-I or OT-II mice that possess a transgenic TCR specific for OVA peptides presented by MHC class I or class II, respectively. Tolerance to OVA did not involve clonal deletion, anergy or an increased regulatory T cell compartment. Rather, CD4+ T cell tolerance resulted from a mechanism of ignorance revealed by their response following OVA immunization. In marked contrast, CD8+ T cells exhibited a loss of OVA-specific cytotoxic activity associated with up-regulation of the immunoregulatory programmed death-1 molecule. Adoptive transfer experiments further showed that OVA expression in skeletal muscle was required to maintain this functional tolerance. These results establish a novel asymmetric model of immunological tolerance to muscle autoantigens involving Ag ignorance for CD4+ T cells, whereas muscle autoantigens recognized by CD8+ T cells results in blockade of their cytotoxic function. These observations may be helpful for understanding the breakage of tolerance in autoimmune muscle diseases.
Starting Page	1
Ending Page	1
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.jimmunol.org/content/181/1/408.full.pdf
PubMed reference number	18566407v1
Volume Number	181
Issue Number	1
Journal	Journal of immunology
Language	English
Access Restriction	Open
Subject Keyword	Anatomical compartments Autoantigens Autoimmune Diseases Clonal Anergy Clonal Deletion Clone Compartment of cell Immune Tolerance Leukemia, B-Cell Skeletal muscle structure T-Cell Receptor Transcriptional Activation
Content Type	Text
Resource Type	Article

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