Polarized Alloantigen Presentation by Airway Epithelial Cells Contributes to Direct CD8+ T Cell Activation in the Airway

Activated T lymphocytes are abundant in the airway during lung allograft rejection. Based on respiratory viral studies, it is the current paradigm that T cells cannot divide in the airway, and that their accumulation in the lumen of the respiratory tract is the exclusive result of recruitment from other sites, such as mediastinal lymph nodes. Here, we show that CD8(+) T cell activation and proliferation can occur in the airway after orthotopic lung transplantation. We also demonstrate that airway epithelium expresses major histocompatibility class I predominantly on the apical surface, both in vitro and in vivo, and initiates CD8(+) T cell responses in a polarized fashion, favoring luminal activation. Our data identify a unique site for CD8(+) T cell activation after lung transplantation, and suggest that attenuating these responses may provide a clinically relevant target.