In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 35 ( 2011-08-30), p. 14602-14607
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1109806108
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2011
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Bookmarklink