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

F Tsushima, S Yao, T Shin, A Flies… - Blood, The Journal …, 2007 - ashpublications.org
F Tsushima, S Yao, T Shin, A Flies, S Flies, H Xu, K Tamada, DM Pardoll, L Chen
Blood, The Journal of the American Society of Hematology, 2007ashpublications.org
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 …
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.
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