Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation

Epidemiology and management of infections after lung transplantation

Lung transplantation has become an accepted treatment for end-stage pulmonary parenchymal and vascular diseases. Infections still are the most common cause of early and late morbidity and mortality in lung transplant recipients. Bacterial infections comprise approximately half of all infectious complications. Cytomegalovirus (CMV) infections and disease have become less frequent, because of prophylaxis with ganciclovir. Because CMV is also involved in the pathogenesis of obliterative bronchiolitis, the frequency of this infection may also reduce the occurrence of this main obstacle to successful lung transplantation. Invasive fungal infections remain a problem, but they have also decreased in frequency because of better control of risk factors such as CMV disease and preemptive antifungal therapy. Nonherpes respiratory viral infections have emerged as a serious problem. Their severity may be reduced by treatment with ribavirin. Meticulous postoperative surveillance, however, is still crucial for the management of lung transplant patients with respect to early detection and treatment of rejection and infection