A VASCULAR SMOOTH MUSCLE-SPECIFIC CD4(-CELL LINE THAT INDUCES PULMONARY VASCULITIS IN MRL-+() T)+ MICE/

We established a T cell line, MV1, specific for rat vascular smooth mu scle antigen from the regional lymph nodes of immunized MRL/Mp-+/+ mic e. Adoptive transfer of MV1 T cells induced vasculitis lesions in the lungs of the syngeneic recipient mice pre-treated with cyclophosphamid e. 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 exp eriments 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 w ith anti-CD3 antibody or antigen-specific activation, killed A20.2J mo use B lymphoma cells. MV1 T cells also killed a CD95 (Fas)-transfected T lymphoma line: but not its parental Fas-negative cell line. These f indings indicate that MV1 T cells killed target cells via a Fas ligand (FasL)/Fas pathway. The cytotoxicity of MV1 T cells may play an impor tant role in the development of vasculitis in this model. Although the antigenic epitopes of MV1 and the lung specificity of vasculitis rema in to be clarified, MV1-induced vasculitis should serve as an experime ntal model of human pulmonary vasculitis.