Figure 2. Mechanism of eosinophil-CD8+ T cell tolerogenic feedback loops in the lung allograft.

Effector CD8+ T cells are the major culprits in allogeneic lung graft rejection. Naïve CD8+ T cells become activated on experiencing alloantigen. This process is associated with TCR engagement and upregulation of differentiation associated molecules, such as PD-1, and the release of Th1 associated cytokines (IFN-γ and TNF-α). The Th1 cytokines released in the microenvironment milieu causes the polarization of eosinophils and their upregulation of PD-L1 and iNOS. PD-L1 binds to PD-1 to provide an immunologic synapse between eosinophil and CD8+ T cells while iNOS catalyzes the synthesis of nitric oxide (NO) that inhibits TCR signaling in a feedback loop (reproduced from data described in^74,75,82).