6mno

Publication Abstract from PubMed

The neonatal thymus generates Foxp3(+) regulatory T (tTreg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tTreg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tTreg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IA(b)-Padi4 with moderate dwell times within a conventional docking orientation are exported as tTreg cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4(+) T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tTreg cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tTreg selection window.

A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3(+) Treg cell development.,Stadinski BD, Blevins SJ, Spidale NA, Duke BR, Huseby PG, Stern LJ, Huseby ES Nat Immunol. 2019 Jun 17. pii: 10.1038/s41590-019-0414-1. doi:, 10.1038/s41590-019-0414-1. PMID:31209405^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.