SECONDARY DISEASE AMONG LETHALLY IRRADIATED MICE RESTORED WITH HEMATOPOIETIC TISSUES FROM NORMAL OR ISO-IMMUNIZED FOREIGN MICE
Journal Article
·
· Brit. J. Exptl. Pathol.
OSTI ID:4755031
Mice lethally irradiated and treated with foreign bone Marrow frequently suffer from secondary disease. The clinical appearance, time of onset, and severity of this wasting disease vary with the donor tissue and the host. In 2 donor-host strain combinations (CBA yields A; A yields CBA) iso-immunization of the donor against antigens of the prospective host has little effect on the syndrome, while addition of spleen cells (normal or iso-immune) to the bone marrow inoculum markedly accelerates and aggravates it. In a 3rd combination (C3H yields CBA), on the other hand. where donor and host are closely related, iso-immunization of the donor accelerates and aggravates the syndrome, while the addition of normal spleen to normal bone marrow actually reduced its incidence and results in better health and longer survival of the hosts. These results suggest that a graft-versus-host reaction in CBA mice treated with normal C3H bone marrow either does not occur or, if it does, is so slight as to lead to negligible damage. The symptoms of this secondary disease must have some other cause, which is largely removed by the injection of lymphoid cells. Secondary wasting disease in these animals may be caused by an inadequate lymphoid system and this in turn may be caused by an inadequate number or failure to mature of lymphoid precursors in the therapeutic bone marrow inoculum. Lymphoid inadequacy could produce secondary disease symptoms by making the chimera susceptible to chronic infections. The failure of normal C3H lymphoid cells to react against the CBA host. and their apparent ability to provide the chimera with an adequate tolerant lymphoid tissue may be due to only the most mature cells in the inoculum being able to give an immune reaction to the weak host antigens. These mature cells might die in the normal course of events before the induction period of the primary immune response against the host could be completed; where the donors were immunized against CBA antigens, and therefore no induction period in the irradiated hosts was necessary, there was a pronounced anti-host reaction. Thus, there are at least 2 causative factors which may operate in secondary disease: an inadequacy of the chimera's lymphoid system and a graft-versus-host immune reaction. The lst factor may produce severe disease even in the absence of the 2nd. (H.H.D.)
- Research Organization:
- Medical Research Council Radiobiological Research Unit, Harwell, Berks, Eng.
- NSA Number:
- NSA-17-005802
- OSTI ID:
- 4755031
- Journal Information:
- Brit. J. Exptl. Pathol., Journal Name: Brit. J. Exptl. Pathol. Vol. Vol: 43
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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