Peripheral regulation of graft-versus-host alloreactivity in mixed chimeric miniature swine

Background. Despite the presence of circulating donor-derived T cells durin g the induction of mixed chimerism across MHC barriers in miniature swine, severe graft-versus-host disease was avoided in the majority of animals. In this study, we investigated the possible roles of recipient and donor lymp hoid populations in the regulation of donor-anti-recipient alloreactivity. Methods. Mixed chimerism. across a full MHC-mismatch barrier was establishe d in miniature swine using a high-dose allogeneic peripheral blood stem cel l protocol. Peripheral blood mononuclear cells from mixed chimeric swine we re co-cultured with naive donor-matched responders and naive recipient-matc hed stimulators in mixed lymphocyte reactions. Results. Peripheral blood mononuclear cells from mixed chimeras inhibited d onor-anti-recipient proliferation. This suppression was radioresistant to 2 5 Gy. Suppression of donor-anti-recipient alloreactivity was not observed i n mixed lymphocyte co-cultures when donor-derived cells were added in the a bsence of recipient-derived cells. Conclusions. These results suggest an association between the presence of a n active and relatively radioresistant cell population, demonstrable in vit ro, and the regulation of graft-versus-host disease across MHC barriers in mixed chimeric miniature swine.