期刊
NATURE IMMUNOLOGY
卷 17, 期 2, 页码 187-195出版社
NATURE PORTFOLIO
DOI: 10.1038/ni.3327
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资金
- US National Institutes of Health [P01 AI35296, F32 AI114050, T32 GM008244, F30 DK093242, T32 AI07313, K99 AI114884]
- Wallin Neuroscience Discovery Fund
- Juvenile Diabetes Research Foundation [2-2011-662]
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. Peptide's 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.
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