American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1-year graft failure and primary graft dysfunction (PGD). ⋯ Recipients of lungs from donors <18 and ≥65 years had increased rates of 1-year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.
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Emerging evidence indicates that complement provides costimulatory signals for murine T cells but whether complement impacts human T cells remains unclear. We observed production of complement activation products C3a and C5a during in vitro cultures of human T cells responding to allogeneic dendritic cells (DC). Both partners expressed the receptors for C3a (C3aR) and C5a (C5aR) and C3aR- and C5aR-antagonists inhibited T cell proliferation. ⋯ Conversely downregulating DC expression of the complement regulatory protein decay-accelerating factor increased immune cell C3a/C5a and augmented T cell proliferation, identifying antigen presenting cells as the dominant complement source. Pharmacological C5aR blockade reduced graft versus host disease (GVHD) scores, prolonged survival, and inhibited T cell responses in NOD scid γc(null) mouse recipients of human peripheral blood mononuclear cells, verifying that the mechanisms apply in vivo. Together our findings unequivocally document that immune cell-derived complement impacts human T cell immunity and provide the foundation for future studies targeting C3aR/C5aR as treatments of GVHD and organ transplant rejection in humans.