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Mohammad Afzal Khan, Fatimah Alanazi, Hala A Ahmed, Almohanna Falah Hasan, Abdullah Altuhami, Abdallah Mohamed Assiri and Dieter Clemens Broering
King Faisal Specialist Hospital and Research Centre, KSA
Posters & Accepted Abstracts: J Clin Cell Immunol
Microvascular loss may be a root cause for chronic rejection in all solid organ transplants, which leads to the bronchiolitis obliterans syndrome (BOS), a fibrotic remodeling resulting in progressive narrowing of small airways. Previous research implicates T regulatory cell (Treg) as a potential mediator of microvascular repair. However, Treg has never been examined as an actual cause of graft hypoxia and ischemia during allograft rejection. We have reported the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to CD4+ T cells mediated rejection. The orthotopic tracheal transplant (OTT) model is ideal for studying the role of Treg mediated immune suppression in the rejection-associated airway hypoxia and ischemia implicated in chronic lung transplant rejection. In this study, we investigated that Treg mediated immune suppression (CD4+ T cells) promotes microvascular reestablishment and thus affects the progress of chronic rejection. Balb/C�?¢�?�?�?�?C57/Bl6 allografts were adoptively transfer with Tregs (1x10^6) I.V. at d0 and allografts were monitored from day-2 to da-28 for tissue pO2, blood perfusion and functional microvasculature during acute rejection. Our data demonstrate that targeted immune suppression by Tregs significantly improves tissue pO2, microvascular flow at day 10 post transplantation, followed by sharp rise in IL-10 and IL-5 gene expression compared to untreated WT controls. However, Tregs treatment in WT is able to significantly (p<0.05) delay acute (from d10 to d14) rejection alone but not able to prevent acute rejection. These findings conclude that protecting airway microvasculature with Treg therapy facilitates microvascular re-establishment and shortens the phase of hypoxia in allograft. These findings can be translated to adjunct therapy in combination with existing transplant therapies especially with low-dose rapamycin (promotes Treg expansion) to improve the efficacy of Treg therapy.