Differential Inactivation of Lymphocytes (Graft-versus-Host Reactions) and Bone Marrow Stem Cells by Heterologous Anti-Mouse Gamma-Globulin Serum,
STANFORD RESEARCH INST MENLO PARK CALIF
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The major obstacle to the clinical application of allogeneic bone marrow transplantation, in the treatment of certain immunologic deficiency disease and of leukemia, is the occurrence of graft-versus-host GVH disease. This syndrome, resulting from donor cell-mediated immunological reactions against tissue antigens of the host is due to the presence of mature, immunologically reactive cells in the marrow inoculum. If these reactive cells could be separated out by physical means or be inactivated specifically, still retaining the viability of the marrow stem cells, it should be possible to prevent GVH disease, following allogeneic bone marrow transplantation. The experimental approach of this research rests on the premise that mature antigen-reactive lymphocytes carry immunoglobulin-like molecules on their surface molecules able to combine with antigen which bears a complementary configurational specificity with that of the immuglobulin moiety. This interaction in turn triggers the metabolic processes leading to blastogenesis, mitosis and the subsequent immune response. On this basis, treatment of mouse antigen-reactive lymphocytes with heterologous anti-mouse gamma-globulin serum would result in the binding of their immunoglobulin antigen-recognition sites by the antiserum, such that these cells would now be immunologically nonreactive.
- Medicine and Medical Research