Emergency granulopoiesis promotes neutrophil-dendritic cell encounters that prevent mouse lung allograft acceptance
D Kreisel, S Sugimoto, J Zhu, R Nava… - Blood, The Journal …, 2011 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2011•ashpublications.org
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 …
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 …
Abstract
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.
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