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.
Bibliographical noteFunding Information:
We thank D. Mueller for reviewing the manuscript; J. Walter and O. Rainwater for technical assistance; P. Lauer (and Aduro Biotech) for the Lm-eGFP strain PL1113. Supported by the US National Institutes of Health (P01 AI35296 to M.K.J. and K.A.H.; F32 AI114050 to D.M.; T32 GM008244 and F30 DK093242 to R.W.N.; T32 AI07313 to J.L.L.; K99 AI114884 to Y.J.L.), the Wallin Neuroscience Discovery Fund (to H.T.O. and M.K.J.) and the Juvenile Diabetes Research Foundation (2-2011-662 to B.T.F.).
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