Prevention of syngeneic graft-versus-host disease by recovery of thymic microenvironment after cyclosporine.

摘要: Following a course of cyclosporine, syngeneic rat radiation chimeras consistently develop GVHD-like syndrome. Correlation the thymic immunopathology with conditions leading to graft-versus-host disease (sGVHD) suggested hypothesis that reconstitution normal microenvironment after CsA is necessary for self-tolerance. When regeneration impaired, as in rats receiving previous mediastinal irradiation, then self-reactive effector cells are not regulated and proceed damage target tissues. Alternately, it could be argued observed abnormalities irrelevant sGVHD. To test primary hypothesis, post-CsA was prevented by total thymectomy unirradiated rats. These developed acute type sGVHD seen at 7 21 days while from CsA-treated sham control group failed Because prior blocks sGVHD, most likely peripheral were derived CsA-altered thymus. The absence indicates thymus led active regulation these stopping CsA. If restored only negative selection, should have also Flow cytometry morphology spleen lymph nodes demonstrated thymectomized rats, like chimeras, experienced significant delay maturation T following In contrast usual model however, did convert chronic importance an abnormal this transition confirmed chimeras. Thymectomy blocked rapid