How specificity for self-peptides shapes the development and function of regulatory T cells.
The cataclysmic disease that develops in mice and humans lacking CD4+ T cells expressing the transcription factor Foxp3 has provided abundant evidence that Foxp3+CD4+ Tregs are required to suppress a latent autoreactivity of the immune system. There is also evidence for the existence of tissue-specific Tregs that can act to suppress regional autoimmune responses, suggesting that Tregs exert their effects, in part, through responding to self-peptides. However, how the immune system generates a repertoire of Tregs that is designed to recognize and direct regulatory function to self-peptides is incompletely understood. This review describes studies aimed at determining how T cell recognition of self-peptide(s) directs Treg formation in the thymus, including discussion of a modified "avidity" model of thymocyte development. Studies aimed at determining how TCR specificity contributes to the ability of Tregs to suppress autoimmune diseases are also discussed.
Simons
Donald M
DM
The Wistar Institute, Philadelphia, PA 19104, USA.
Picca
Cristina Cozzo
CC
Oh
Soyoung
S
Perng
Olivia A
OA
Aitken
Malinda
M
Erikson
Jan
J
Caton
Andrew J
AJ
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell