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AbstractObliterative bronchiolitis (OB) is a form of chronic rejection after lung transplantation. Lentiviral vectors (LVs) facilitate long-term gene transduction in many tissues and organs. We hypothesized that lentiviral gene transfer of interleukin (IL)-10, a potent immune-modulating cytokine, to the lung could modulate the alloimmune responses in the lung after transplantation. C57BL6 mice received LVs encoding luciferase, enhanced green fluorescent protein (eGFP), or human IL-10 (huIL-10) through airways and underwent repeated bioluminescent imaging, immunofluorescence imaging, or ELISA of lung tissues, respectively. Luciferase activities peaked at day 7 and were stable after day 28 to over 15 months. eGFP staining demonstrated LV-mediated gene transduction mainly in alveolar macrophages. LV-huIL-10 delivery resulted in stable long-term expression of huIL-10 in the lung tissue (average 3.66 pg/mg at 1 year). Intrapulmonary allograft tracheal transplantation (BALBc→C57BL6) was used as a model of OB. LV-huIL-10 or LV-eGFP were delivered 7 days before transplantation and compared with no LV-transfection group. Allograft airways at day 28 were almost completely obliterated in all the groups. However, at day 42, allograft airways treated with LV-huIL-10 showed a spectrum of attenuation in airway fibrosis ranging from complete obliteration through bubble-like partial opening to complete patency with epithelial coverage in association with a significantly reduced obliteration ratio compared with the other groups (p<0.05). In conclusion, lentivirus-mediated gene transduction is useful in achieving long-term transgene expression in the lung. Long-term IL-10 expression has the potential to attenuate allograft airway obliteration. LV-mediated gene therapy could be a useful strategy to prevent or treat OB after lung transplantation. [ABSTRACT FROM AUTHOR]

AbstractAdoptive T cell therapy is aimed at overcoming constraints of the endogenous immune response. In patients with malignancies, this approach is based on the possibility of administering sufficient numbers of tumor-reactive lymphocytes under conditions in which they will promote a therapeutic response. Although this strategy is potentially applicable to a vast number of malignancies, its efficacy, to date, has been limited. This is likely related to several factors including an insufficient persistence and reactivation of infused cells, insufficient tumor infiltration, and the presence of an immunosuppressive environment. Here, we review the importance of pretransplantation host conditioning and posttransplantation strategies that have been shown to contribute to the therapeutic efficacy of infused T lymphocytes. [ABSTRACT FROM AUTHOR]