In vitro determination of self-reactivity in the early postcyclosporine period.

摘要: Abstract Since cyclosporine A(CsA) was introduced into transplantation medicine to prevent graft-versus-host disease (GvHD) as well graft rejection, side-effects became obvious. When CsA is given and withdrawn GvHD-like symptoms can occur even in an autologous setting. To understand this mechanism we tested the allo- self-reactivity of murine spleen lymphocytes vitro assay. Mice four different strains with two distinct MHC class I backgrounds (H-2 d H-2 k ) were treated 60 mg/kg/day intraperiteonally for ten days. In attempt examine possibility that CsA-induced autoimmunity requires presence thymus, half these four- six-week-old mice also thymectomized prior treatment. Within one day after stopped, all received during treatment showed reactivity against self-MHC-bearing cells. This demonstrated a primary stimulation assay followed by chromium-release -anti-H-2 ). However, alloreactivity suppressed. At point time, no natural killer (NK) activity detectable any CsA-treated mice. The days stopping CsA, autoreactivity longer mouse strain, whether or not, whereas NK finally recovered. phenomena self-reactivity, which occurred between 10 withdrawal, could be adoptively transferred from syngeneic reactive T cell populations identical sublethally irradiated recipients autoreactive cells died within 10–20 days, showing clinical signs pseudo GvHD (pGvHD). Irradiated control not receiving self-reactive cells, but irradiated, survived without complications. Our results suggest existence MHC-restricted which, under normal immunological conditions, are regulated probably nonfunctional vivo . other immunomodulatory manipulations may interfere maintainance self-tolerance lead activation role thymus at stage selection clear, since show has effect on mature periphery.