Thymocyte deletion can bias Treg formation toward low-abundance self-peptide.
Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg as they develop intrathymically, but how these alternative developmental fates are specified based on interactions with self-peptide(s) is not understood. We show here that thymocytes expressing an autoreactive TCR can be subjected to varying degrees of deletion that correlate with the amount of self-peptide. Strikingly, among thymocytes that evade deletion, similar proportions acquire Foxp3 expression. These findings provide evidence that Foxp3+ Treg can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self-peptide, and that deletion and Treg formation can act together to bias the Treg repertoire toward low-abundance self-peptide(s).
Picca
Cristina Cozzo
CC
The Wistar Institute, Philadelphia, PA 19104, USA.
Oh
Soyoung
S
Panarey
Laura
L
Aitken
Malinda
M
Basehoar
Alissa
A
Caton
Andrew J
AJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D010455:Peptides; D011948:Receptors, Antigen, T-Cell