title: CD4⁺CD25⁺Foxp3⁺ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion.
abstract: CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are generated during thymocyte development and play a crucial role in preventing the immune system from attacking the body's cells and tissues. However, how the formation of these cells is directed by T-cell receptor (TCR) recognition of self-peptide:major histocompatibility complex (MHC) ligands remains poorly understood. We show that an agonist self-peptide with which a TCR is strongly reactive can induce a combination of thymocyte deletion and CD4(+)CD25(+)Foxp3(+) Treg cell formation in vivo. A weakly cross-reactive partial agonist self-peptide could similarly induce thymocyte deletion, but failed to induce Treg cell formation. These studies indicate that CD4(+)CD25(+)Foxp3(+) Treg cell formation can require highly stringent recognition of an agonist self-peptide by developing thymocytes. They also refine the "avidity" model of thymocyte selection by demonstrating that the quality of the signal mediated by agonist self-peptides, rather than the overall intensity of TCR signaling, can be a critical factor in directing autoreactive thymocytes to undergo CD4(+)CD25(+)Foxp3(+) Treg cell formation and/or deletion during their development.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cozzo Picca
authors.forename: Donald M
authors.initials: DM
authors.lastname: Simons
authors.forename: Soyoung
authors.initials: S
authors.lastname: Oh
authors.forename: Malinda
authors.initials: M
authors.lastname: Aitken
authors.forename: Olivia A
authors.initials: OA
authors.lastname: Perng
authors.forename: Christina
authors.initials: C
authors.lastname: Mergenthaler
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kropf
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
mesh_terms: D000818:Animals; D006649:Histocompatibility Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D006649:Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell