CD4+ T Cells Sensitized by Vascular Smooth Muscle Induce Vasculitis, and Interferon Gamma Is Critical for the Initiation of Vascular Pathology

Primary vasculitis is the result of idiopathic inflammation m blood vessel walls T cells are believed to play a critical role but the nature of the pathological T cell response remains obscure In this study we provide evidence that CD4(+) T lymphocytes activated in the presence of syngeneic vascular smooth muscle cells were sufficient to induce vasculitic lesions after adoptive transfer to recipient mice Additionally the disease is triggered m the absence of antibodies in experiments in which both the donors of stimulated lymphocytes and the transfer recipients were mice that were deficient in B cells Tracking and proliferation of the transferred cells and their cytokine profiles were assessed by fluo rescence tagging and flow cytometry Proliferating CD4+ T cells were evident 3 days after transfer corresponding to the occurrence of vasculitic le slops in mouse lungs The transferred T lymphocytes exhibited Th1 and Th17 cytokine profiles and minimal Th2 However, 1 week after vasculitis in duction effector functions could be successfully recalled in Th1 cells but not in Th17 cells Additionally in the absence of constitutive interferon gamma expression T cells sensitized by vascular smooth muscle cells failed to induce vasculitis In conclusion our results show that Th1 cells play a key role in eliciting vasculitis m this murine model and that induction of the disease is possible m the absence of pathogenic antibodies (Am J Pathol 2010 177 3215-3223; DOI 10 2353/ajpath 2010 090985)