Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d) prior to transplanting into C57BL/6 mice (H-2b), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.Lung transplantation is the only therapeutic modality for many patients with end stage lung disease. However, the lung is rejected more often than other grafts and the five year survival is only 50% which is the worst of all solid organs transplants. Many pathologies contribute to the graft dysfunction post transplantation and include primary graft dysfunction (PGD) [1,2], acute rejection and bronchiolitis obliterans syndrome (BO/BOS). All of these are believed to have a component of immune activation resulting in either allo- or autoimmunity that contributes to graft pathology.Immune activation post lung transplant may be mediated by one of three pathways, direct, indirect or semi-direct [3]. The direct pathway, i.e., mediated by donor derived DCs interacting with recipient T cells, is believed to be the predominant pathway involved in alloimmune activation that leads to rejection in the early post transplant period. Unlike other solid organ allografts, t