The mechanisms by which innate immune signals regulate alloimmune responses 
remain poorly understood. In the present study, we show by intravital 2-photon 
microscopy direct interactions between graft-infiltrating neutrophils and donor 
CD11c(+) dendritic cells (DCs) within orthotopic lung allografts immediately 
after reperfusion. Neutrophils isolated from the airways of lung transplantation 
recipients stimulate donor DCs in a contact-dependent fashion to augment their 
production of IL-12 and expand alloantigen-specific IFN-γ(+) T cells. DC IL-12 
expression is largely regulated by degranulation and induced by TNF-α associated 
with the neutrophil plasma membrane. Extended cold ischemic graft storage 
enhances G-CSF-mediated granulopoiesis and neutrophil graft infiltration, 
resulting in exacerbation of ischemia-reperfusion injury after lung 
transplantation. Ischemia reperfusion injury prevents immunosuppression-mediated 
acceptance of mouse lung allografts unless G-CSF-mediated granulopoiesis is 
inhibited. Our findings identify granulopoiesis-mediated augmentation of 
alloimmunity as a novel link between innate and adaptive immune responses after 
organ transplantation.