Mouse parvovirus infection potentiates allogeneic skin graft rejection and induces syngeneic graft rejection

Background. The recently identified autonomous mouse parvovirus designated mouse parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects lymphoid tissues, interferes with the ability of cloned T cells to proliferate, and exhibits immunomodulatory properties. As a consequence of these findings, the present studies were undertaken to characterize further the immunomodulatory effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro. Methods. To evaluate the effect of MPV-1 infection on CD8(+) T cell-mediated responses, BALB/c-H2(dm2) mice were infected after transplantation of allogeneic BALB/c skin. Results. MPV-1 potentiated the rejection of allogeneic skin grafts. This potentiation was not a result of virus infecting the cellular or vascular component of the graft as determined by in situ hybridization, but was mediated by T cells. However, the proliferative capacity of alloantigen-reactive lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also induced the rejection of syngeneic skin grafts, and T cells from these infected graft-sensitized mice lysed syngeneic P815 target cells. Conclusions. These results suggest that MPV-1 infection of skin-grafted mice may disrupt normal mechanisms of peripheral tolerance and provide a unique model to study virus-induced autoimmunity.