Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide.
Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR) to undergo selection to become CD4+CD25+ regulatory T cells. Selection of CD4+CD25+ thymocytes appears to require a TCR with high affinity for a self peptide because thymocytes that bear TCRs with low affinity do not undergo selection into this pathway. Our findings indicate that specificity for self-peptides directs the selection of CD4+CD25+ regulatory thymocytes by a process that is distinct from positive selection and deletion.
Jordan
M S
MS
The Wistar Institute, Philadelphia, PA 19104, USA.
Boesteanu
A
A
Reed
A J
AJ
Petrone
A L
AL
Holenbeck
A E
AE
Lerman
M A
MA
Naji
A
A
Caton
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D017634:Self Tolerance; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2