Induction of vasculitis by vascular smooth muscle-specifc T cells and analysis of its mechanism

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We established a T-cell line, MV1, specific for rat vascular smooth muscle antigen from the regional lymph nodes of immunized MRL/Mp-+/+ mice. Adoptive transfer of MV1 T cells induced vasculitis lesions in the lungs of the syngeneic recipient mice pre-treated with cyclophosphamide. Flow cytometric analysis showed that MV1 was a CD4+ T cell line. The T cells proliferated in the presence of the vascular smooth muscle antigen and mitomycin C-treated syngeneic spleen cells. The cross experiments using an ovalbumin-specific T-cell line demonstrated that MV1 was specific for vascular smooth muscle antigen. The antigen-specific proliferation of MV1 was CD4 dependent, which was consistent with the flow cytometric analysis. In addition, MV1 T cells, upon activation with anti-CD3 antibody or antigen-specific activation, killed A 20.2J mouse B lymphoma cells. MV1 T cells also killed a CD95 (Fas) -transfected T lymphoma line, but not its parental Fas-negative cell line. These findings indicated that MV1 T cells killed target cells via a Fas ligand (FasL) /Fas pathway. The cytotoxicity of MV1 T cells may play an important role in the development of the vasculitis in this model. Although the antigenic epitopes of MV1 and the lung specificity of the vasculitis remain to be clarified, MV1-induced vasculitis should serve as an experimental model of human pulmonary vasculitis.