Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy.
Blood. 2007 Feb 8
Tsushima F, Yao S, Shin T, Flies A, Flies S, Xu H, Tamada K, Pardoll DM, Chen L.
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Although self-reactive T cell precursors can be eliminated upon recognition of self-antigen presented in thymus, this central tolerance process is often incomplete and additional mechanisms are required to prevent autoimmunity. Recent studies implicate 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. |
