T cells presenting viral antigens or autoantigens induce cytotoxic T cell anergy.

Autor:	Blachère NE; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Howard Hughes Medical Institute, New York, New York, USA., Orange DE; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Division of Rheumatology, Hospital for Special Surgery, New York, New York, USA.; New York Genome Center, New York, New York, USA., Gantman EC; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; CHDI Management/CHDI Foundation, New York, New York, USA., Santomasso BD; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Memorial Sloan-Kettering Cancer Center, New York, New York, USA., Couture GC; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA., Ramirez-Montagut T; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Genentech, Inc., South San Francisco, California, USA., Fak J; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA., O'Donovan KJ; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Department of Chemistry and Life Sciences, United States Military Academy, West Point, New York, USA., Ru Z; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA., Parveen S; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA., Frank MO; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; New York Genome Center, New York, New York, USA., Moore MJ; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Regeneron Pharmaceuticals, Tarrytown, New York, USA., Darnell RB; Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.; Howard Hughes Medical Institute, New York, New York, USA.; New York Genome Center, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2017 Nov 02; Vol. 2 (21). Date of Electronic Publication: 2017 Nov 02.
DOI:	10.1172/jci.insight.96173
Abstrakt:	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.
Databáze:	MEDLINE
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