T cells presenting viral antigens or autoantigens induce cytotoxic T cell anergy Journal Article


Authors: Blachère, N. E.; Orange, D. E.; Gantman, E. C.; Santomasso, B. D.; Couture, G. C.; Ramirez-Montagut, T.; Fak, J.; O'Donovan, K. J.; Ru, Z.; Parveen, S.; Frank, M. O.; Moore, M. J.; Darnell, R. B.
Article Title: T cells presenting viral antigens or autoantigens induce cytotoxic T cell anergy
Abstract: In the course of modeling the naturally occurring tumor immunity seen in patients with paraneoplastic cerebellar degeneration (PCD), we discovered an unexpectedly high threshold for breaking CD8+ cytotoxic T cell (CTL) tolerance to the PCD autoantigen, CDR2. While CDR2 expression was previously found to be strictly restricted to immune-privileged cells (cerebellum, testes, and tumors), unexpectedly we have found that T cells also express CDR2. This expression underlies inhibition of CTL activation; CTLs that respond to epithelial cells expressing CDR2 fail to respond to T cells expressing CDR2. This was a general phenomenon, as T cells presenting influenza (flu) antigen also fail to activate otherwise potent flu-specific CTLs either in vitro or in vivo. Moreover, transfer of flu peptide-pulsed T cells into flu-infected mice inhibits endogenous flu-specific CTLs. Our finding that T cells serve as a site of immune privilege, inhibiting effector CTL function, uncovers an autorepressive loop with general biologic and clinical relevance. © 2017 American Society for Clinical Investigation. All rights reserved.
Journal Title: JCI Insight
Volume: 2
Issue: 21
ISSN: 2379-3708
Publisher: Amer Soc Clinical Investigation Inc  
Date Published: 2017-11-02
Start Page: e96173
Language: English
DOI: 10.1172/jci.insight.96173
PUBMED: 29093272
PROVIDER: scopus
PMCID: PMC5752293
DOI/URL:
Notes: Article -- Source: Scopus
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