Quantitative impact of thymic selection on Foxp3 + and Foxp3 - subsets of self-peptide/MHC class II-specific CD4 + T cells

James J. Moon, Pradyot Dash, Thomas H. Oguin, Jennifer L. McClaren, H. Hamlet Chu, Paul G. Thomas, Marc Jenkins

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

It is currently thought that T cells with specificity for self-peptide/ MHC (pMHC) ligands are deleted during thymic development, thereby preventing autoimmunity. In the case of CD4 + T cells, what is unclear is the extent to which self-peptide/MHC class II (pMHCII)-specific T cells are deleted or become Foxp3 + regulatory T cells. We addressed this issue by characterizing a natural polyclonal pMHCII-specific CD4 + T-cell population in mice that either lacked or expressed the relevant antigen in a ubiquitous pattern. Mice expressing the antigen contained one-third the number of pMHCII-specific T cells as mice lacking the antigen, and the remaining cells exhibited low TCR avidity. In mice lacking the antigen, the pMHCII-specific T-cell population was dominated by phenotypically naive Foxp3 - cells, but also contained a subset of Foxp3 + regulatory cells. Both Foxp3 - and Foxp3 + pMHCII-specific T-cell numbers were reduced in mice expressing the antigen, but the Foxp3 + subset was more resistant to changes in number and TCR repertoire. Therefore, thymic selection of self-pMHCII-specific CD4 + T cells results in incomplete deletion within the normal polyclonal repertoire, especially among regulatory T cells.

Original languageEnglish (US)
Pages (from-to)14602-14607
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number35
DOIs
StatePublished - Aug 30 2011

Keywords

  • T-cell receptor
  • Tetramer
  • Tolerance
  • Transgenic
  • Treg

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