Role of the thymus in control of autoreactivity or allotolerance in syngeneic and allogeneic bone marrow chimeras treated with bacterial adjuvants.
Thy-1-bone marrow (BM) cells from C57BL/6 (B6) mice were transferred into thymectomized or non-thymectomized syngeneic B6----B6, allogeneic B6----C3H or semiallogeneic B6----(B6 X C3H)F1, irradiated mice, after which bacterial substances (bacillus Calmette Guérin [BCG] or Bordetella pertussis [Bp]) were administered within 3 days. The regulation of reactivity toward the host environment, i.e., autoresponsiveness in B6----B6 and allotolerance in B6---C3H, was investigated by monitoring a graft-vs-host (GvH)-like wasting syndrome, as well as the in vitro responsiveness of spleen cells from the reconstituted mice in a mixed leukocyte culture/cell-mediated lysis (MLC/CML) assay. The BCG-treated B6----B6 recipients developed a wasting syndrome and MLC/CML reactivity toward syngeneic target cells within 7 wk. This was never observed in BCG-treated but otherwise normal (i.e., nonreconstituted) mice, nor was it seen in any bone marrow chimeras that had been left without BCG treatment, irrespective of host/donor combination or thymectomy. The development of wasting syndrome as well as autoreactivity in BCG-treated B6----B6 mice could be prevented by thymectomizing the recipients before reconstitution or co-cultivating the donor BM cells with syngeneic spleen cells before reconstitution of nonthymectomized recipients. In the allogeneic or semiallogeneic combinations, the BCG treatment resulted in a wasting syndrome and CML/MLC reactivity toward C3H or (C3H X B6)F1 host-derived cells irrespective of thymic presence or absence. No breakdown of allotolerance, however, was retarded in the thymectomized mice, and it could be prevented by co-cultivation of donor BM cells with splenocytes of recipient genotype only if the cells were used to reconstitute thymectomized recipients. The breakdown of allotolerance in B6----C3H chimera was never accompanied by autoreactivity against B6 target cells. It is concluded that induction of autoreactivity and GvH in BCG-treated syngeneic BM chimeras, probably reflecting the breakdown of autotolerance, is strictly thymus dependent. In contrast, induction of anti-host reactivity in BCG-treated allogeneic chimeras may occur in the absence of a thymus and without concomitant autoreactivity, suggesting two independent levels of controls: one that is thymus dependent for the breakdown of auto- as well as allotolerance, and one that is thymus independent, unique for the breakdown of allotolerance.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001500:BCG Vaccine / Q000494:pharmacology; D016026:Bone Marrow Transplantation; D001886:Bordetella pertussis / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D006087:Graft vs Host Reaction; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D013950:Thymus Gland / Q000276:immunology*
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D001500:BCG Vaccine; D007519:Isoantigens