Dendritic cells overexpressing Fas-ligand induce pulmonary vasculitis in mice

摘要: Dendritic cells (DC) genetically engineered to express Fas (CD95) ligand (FasL-DC) have been proposed as immunotherapeutic tools induce tolerance allografts. However, we and others recently showed that FasL-DC elicit a vigorous inflammatory response involving granulocytes can promote Th1-type CD4+ cytotoxic CD8+ T lymphocytes. This prompted us evaluate the pathology induced by intravenous injection of in mice. We observed obtained after retroviral gene transfer bone marrow precursors derived from Fas-deficient C57Bl/6 mice massive pulmonary inflammation pleuritis one day single Two months later, all presented granulomatous vasculitis small medium sized vessels, alveolar haemorrhage pleuritis. In these lesions, apoptotic bodies were found large number. Anti-neutrophilic cytoplasmic anti-myeloperoxidase autoantibodies not detected. study documents causes severe lung vasculitis. new animal model for is inducible, highly reproducible shares many features with human Wegener granulomatosis. may be an appropriate tool further investigate pathogenesis test therapeutic strategies. Moreover, our findings highlight potential complications FasL-DC-based immunotherapy.