Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy

• Published in: Blood Vol. 110; no. 1; pp. 180 - 185
• Main Authors: Tsushima, Fumihiko, Yao, Sheng, Shin, Tahiro, Flies, Andrew, Flies, Sarah, Xu, Haiying, Tamada, Koji, Pardoll, Drew M., Chen, Lieping
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-07-2007; The Americain Society of Hematology; American Society of Hematology
• Series: Immunobiology
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigen specific factors; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Antigens, Differentiation - metabolism; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-H1 Antigen; Biological and medical sciences; Clonal Anergy - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Lymph Nodes - cytology; Lymphocyte Activation - immunology; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Peptides - immunology; Peptides - metabolism; Programmed Cell Death 1 Receptor; Regulatory factors and their cellular receptors; Self Tolerance - immunology; T-Lymphocytes - immunology; Up-Regulation - genetics; Anergy; Rodentia; Cellular immunity; Costimulatory molecule; In vivo; Signal transduction; B7-H1 Molecule; Vertebrata; Mammalia; Mouse; Animal; T-Lymphocyte; Reversibility; Initiation; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-11-060087

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.