Isolation of vascular smooth muscle antigen-reactive CD4(+)alpha beta Th1 clones that induce pulmonary vasculitis in MRL/Mp-Fas(+/+) mice

摘要

Here, we established Cb4(+)alpha beta Th1 clones specific for rat vascular smooth muscle antigen (VSMAg) that induced vasculitis lesions in the lungs of MRL/Mp-Fas(+/+) mice following adoptive transfer. Six different T cell clones, MV1b1 (V beta 1), MV1b4 (V beta 4), MV1b8.3 (V beta 8.3), MV1b61 (V beta 6), MV1b62 (V beta 6), and MV1b63 (V beta 6), were isolated from the MV1 T cell line from the regional lymph nodes of immunized MRL/Mp-Fas(+/+) mice; the three (V beta 6) clones had unique CDR3 amino acid sequences. Following stimulation with VSMAg-pulsed antigen presenting cells, MV1b61 and MV1b62 failed to secrete interferon-gamma and tumor necrosis factor-alpha, although the other four clones secreted high levels of both cytokines. In adoptive transfer experiments, MV1b61 and MV1b62 did not induce organ involvement including pulmonary vasculitis. In contrast, MV1b1, MV1b4, MV1b8.3, and MV1b63 induced perivascular mononuclear cell infiltration in pulmonary small arteries. These clones may provide useful tools for investigating the underlying mechanisms of vasculitis syndromes and for developing therapeutic strategies. (C) 2016 Elsevier Inc. All rights reserved.