Opposing peripheral fates of tissue-restricted self antigen-specific conventional and regulatory CD4+ T cells.
Eur J Immunol
; 50(1): 63-72, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31580477
ABSTRACT
The development of self antigen-specific T cells is influenced by how the self antigen is expressed. Here, we created a mouse in which a model self antigen is conditionally expressed in different tissue environments. Using peptideMHCII tetramer-based cell enrichment methods, we examined the development of corresponding endogenous self antigen-specific CD4+ T cell populations. While ubiquitous self antigen expression resulted in efficient deletion of self antigen-specific T cells in the thymus, some tissue-restricted expression patterns resulted in partial deletion of the population in peripheral lymphoid organs. Deletion specifically affected Foxp3- conventional T cells (Tconv) with a bias towards high avidity TCR expressing cells in the case of thymic, but not peripheral deletion. In contrast, Foxp3+ Treg exhibited elevated frequencies with increased TCR avidity. T cells surviving deletion were functionally impaired, with Tconv cells exhibiting more impairment than Tregs. Collectively, our results illustrate how postthymic recognition of tissue-restricted self antigens results in opposing developmental fates for Tconv and Treg cell subsets.
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MEDLINE
Assunto principal:
Autoantígenos
/
Linfócitos T Reguladores
/
Tolerância a Antígenos Próprios
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article