Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2011-08, Vol.108 (35), p.14602-14607

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.