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Role of the thymus in control of autoreactivity or allotolerance in syngeneic and allogeneic bone marrow chimeras treated with bacterial adjuvants.

K. Taniguchi,H. Gondo,K. Nomoto

Published 1984 in Journal of Immunology

ABSTRACT

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.

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