Induction of Allospecific Cytotoxic T Cells by Virus Infections In Vivo

Abstract

Rejection of implanted tissue grafts is due to T cell responses against allogeneic histocompatibility antigens. Graft rejection was for some time thought to be mediated by helper T cells, but more recent evidence indicates that cytotoxic T cells infiltrate grafts and probably play a major role in rejection (Ascher et al. 1981; Tyler et al. 1984). Graft rejection in transplant patients sometimes occurs following infections with viruses, most notably human cytomegalovirus (Simmons et al. 1974; May et al. 1978) (HCMV) and influenza virus (Briggs et al. 1972), and it has been suggested that these virus infections might help to stimulate immune responsiveness against the foreign tissue (Gaston and Waer 1985). Recently, several T cell lines bearing cross-reactivity between virus-modified syngeneic MHC antigens and allogeneic MHC antigens have been isolated, leading to the hypothesis that virus-specific T cells bearing cross-reactivity with alloantigens may provide the mechanism for the virus-induced graft rejection (Gaston and Waer 1985; Braciale et al. 1981; Sheil et al. 1987). This hypothesis invokes specific cross-reactive clones as mediators of graft rejection, in contrast to a more generalized less specific biological response modifier effect.