Fetal exposure to high-avidity TCR ligand enhances expansion of peripheral T regulatory cells

Ping Yu, Cara L. Haymaker, Rohit D. Divekar, Jason S. Ellis, John Hardaway, Renu Jain, Danielle M. Tartar, Christine M. Hoeman, Jason A. Cascio, Austin Ostermeier, Habib Zaghouani*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Lately, it has become clear that regulatory T cells (Tregs) play a major role in the maintenance of peripheral tolerance and control of autoimmunity. Despite these critical functions, the process underlying the development of Tregs remains largely undefined. Herein, altered peptide ligand (APL) variants derived from the proteolipid protein-1 (PLP1) epitope were expressed on immu-noglobulins (Igs) and the resulting Ig-APLs were used to deliver the APLs from mother to fetus through the maternal placenta to influence thymic T cell selection. This delivery system was then adapted to the SJL/J mouse, a strain that expresses only the DM20 form of PLP, which lacks the dominant PLP1 epitope in the thymus during fetal and neonatal development. This model, which restores thymic T cell selection for PLP1, was then used to determine whether affinity plays a role in the development of Tregs. The findings show that fetal exposure to low-affinity peptide ligand was unable to drive development of Tregs while variants with higher affinity to the TCR resulted in significant seeding of the periphery with mature, naive Tregs. Thus, contrary to pathogenic T cells, Tregs require avid TCR-ligand interaction to undergo thymic development and maturation.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalJournal of Immunology
Volume181
Issue number1
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yu, P., Haymaker, C. L., Divekar, R. D., Ellis, J. S., Hardaway, J., Jain, R., Tartar, D. M., Hoeman, C. M., Cascio, J. A., Ostermeier, A., & Zaghouani, H. (2008). Fetal exposure to high-avidity TCR ligand enhances expansion of peripheral T regulatory cells. Journal of Immunology, 181(1), 73-80. https://doi.org/10.4049/jimmunol.181.1.73