Transplant arteriosclerosis in humanized mice reflects chronic lung allograft dysfunction and is controlled by regulatory T cells

Abstract

Objective: Chronic lung allograft dysfunction (CLAD) is a severe complication of lung transplantation limiting long-term survival. We studied correlations between CLAD after clinical lung transplantation and leukocyte-mediated development of transplant arteriosclerosis (TA) in a humanized mouse model. The pericardiophrenic artery was procured from surplus tissue of donor lungs (n ¼ 22) transplanted in our clinical program and was implanted into the abdominal aorta of immune-deficient mice.Methods: Allogeneic human peripheral blood mononuclear cells (PBMCs) had been procured 1 day after lung transplantation from the respective recipients with or without enriching for CD4 þ CD25 high T cells were used. TA was assessed in mice 28 days later by histology. The respective clinical lung recipients were later divided into 2 groups. Eight patients (36.3%) had developed CLAD 23 AE 5 months after lung transplantation, whereas the remaining 14 (63.6%) did not develop CLAD within 25 AE 5 months.See Commentaries on pages 2538 and 2540.Long-term survival after lung transplantation is compromised by the development of chronic lung allograft dysfunction (CLAD), resulting from recurrent and compounding alloimmune infections and other insults and is characterized by neutrophil inflammation, fibrosis, respiratory failure, and death. Ten-year survival following From the a Division of Cardiac,

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“…Interestingly, histological changes in the artery were associated with development of chronic lung allograft dysfunction in the patient, indicating the presence of alloreactive T cells at time of transplant. 225 Such models could provide a method for developing customized patient-specific therapies.…”