Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy.
Although self-reactive T-cell precursors can be eliminated upon recognition of self-antigen presented in the thymus, this central tolerance process is often incomplete, and additional mechanisms are required to prevent autoimmunity. Recent studies indicates that the interaction between B7-H1 and its receptor PD-1 on activated T cells plays an important role in the inhibition of T-cell responses in peripheral organs. Here, we show that, before their exit to the periphery, T cells in lymphoid organs rapidly up-regulate PD-1 upon tolerogen recognition. Ablation of the B7-H1 and PD-1 interaction when T cells are still in lymphoid organs prevents anergy. Furthermore, blockade of B7-H1 and PD-1 interaction could render anergic T cells responsive to antigen. Our results thus reveal previously unappreciated roles of B7-H1 and PD-1 interaction in the control of initiation and reversion of T-cell anergy.
Tsushima
Fumihiko
F
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Yao
Sheng
S
Shin
Tahiro
T
Flies
Andrew
A
Flies
Sarah
S
Xu
Haiying
H
Tamada
Koji
K
Pardoll
Drew M
DM
Chen
Lieping
L
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D060890:B7-H1 Antigen; D017635:Clonal Anergy / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics
D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor