Letter: Irradiated Kveim suspensions.
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Biomedical subjects
Publications and source records attributed to R J Rees.
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Intact human bone marrow cells from 7 patients with myelomatosis were inoculated intravenously into adolescent CBA mice rendered immunologically deficient by thymectomy followed by total body irradiation (600 rad). Each inoculum of human myeloma marrow cells and subsequent passages of intact mouse marrow and spleen cells resulted in the presence of morphological changes in the marrow, spleen and peripheral blood of a proportion of these mice which were closely similar to those seen in the human donor. A substantial amount of human immunoglobulin (IgG and IgA) was detected in the sera of some of the mice showing morphological changes. Mice prepared identically but remaining uninoculated or receiving intact human bone marrow cells from 3 patients with no evidence of haematological malignancy showed none of these changes when examined after similar intervals.There are at least 3 possible explanations for these findings: in mice receiving human myeloma marrow cells they might be accounted for by the persistence and replication of these cells in an immunologically deficient host. In mice receiving a first, second or third passage of abnormal mouse marrow and spleen cells they might similarly be accounted for by the survival and multiplication of a stem cell secreting both mouse and human immunoglobulins. Alternatively, the mouse stem cells may in some way have been transformed following infection by a transmissible agent originally present in the myeloma donor marrow cells.
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Adult CBA mice thymectomized, treated with antilymphocytic globulin (ALG) and inoculated with human leprosy organisms were accidentally infected with polyoma virus and all developed tumours. After cessation of ALG administration, some animals were given spleen cells from syngeneic donors immunized with polyoma virus; none developed tumours. Similar results were obtained in mice deliberately infected with polyoma virus but not with leprosy organisms. Passive transfer of antibody before but not after virus inoculation prevented tumour formation in immunosuppressed recipients. Virus infection in thymectomized, lethally irradiated and bone marrow reconstituted mice resulted in only a very low incidence of tumours. These results emphasize the role of immunological surveillance in preventing polyoma tumour formation under natural conditions.
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