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Nat Immunol. 2016 Feb;17(2):187-95. doi: 10.1038/ni.3327. Epub 2016 Jan 4.

Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.

Author information

1
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
2
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
3
Diabetes Center, University of California San Francisco, San Francisco, California, USA.
4
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
5
Department of Laboratory Medicine and Pathology, Institute for Translational Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

Abstract

Studies of repertoires of mouse monoclonal CD4(+) T cells have revealed several mechanisms of self-tolerance; however, which mechanisms operate in normal repertoires is unclear. Here we studied polyclonal CD4(+) T cells specific for green fluorescent protein expressed in various organs, which allowed us to determine the effects of specific expression patterns on the same epitope-specific T cells. Peptides presented uniformly by thymic antigen-presenting cells were tolerated by clonal deletion, whereas peptides excluded from the thymus were ignored. Peptides with limited thymic expression induced partial clonal deletion and impaired effector T cell potential but enhanced regulatory T cell potential. These mechanisms were also active for T cell populations specific for endogenously expressed self antigens. Thus, the immunotolerance of polyclonal CD4(+) T cells was maintained by distinct mechanisms, according to self-peptide expression patterns.

PMID:
26726812
PMCID:
PMC4718891
DOI:
10.1038/ni.3327
[Indexed for MEDLINE]
Free PMC Article

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