July 20, 1999 Researchers at the University of Pennsylvania Medical Center have devised a safer, more effective strategy for bone marrow transplantation that does not require the use of drugs that globally suppress the immune system. A report on the new technique, demonstrated in mice, appears in the July 16 issue of Science.
Transplantation of bone marrow, which gives rise to all types of blood cells in the body, including immune system cells, is useful in treating cancers of the blood and inherited blood disorders. Because it is the source of the cells that constitute the immune system, however, bone marrow transplantation sometimes leads to a potentially quite serious condition called graft-versus-host disease, or GVHD, in which T cells produced by the donor marrow attack the host, i.e., the patient receiving the transplant.
For this reason, powerful drugs that suppress the immune system, primarily by paralyzing T cells, are given to bone marrow transplant recipients to control GVHD. Immune suppression carries its own costs, however, leaving the patient vulnerable to infections and other problems.
The new approach used by the Penn scientists involves inactivating a subset of immune-system cells in the transplant recipient called antigen-presenting cells, or APCs. Although the patient's existing bone marrow is destroyed prior to transplantation - largely to preclude GVHD - APCs originating from that marrow continue to circulate in the patient's blood. Those APCs serve as the trigger for T cells produced by the newly received bone marrow to attack cells in the patient. When these APCs were disabled, however, GVHD was entirely prevented.
"Most techniques for immunosuppression are based upon paralyzing T cells," says Stephen G. Emerson, MD, chief of the division of hematology-oncology, professor of medicine, and senior author on the report. "They're global, and they have serious limitations. Targeting antigen-presenting cells, however, provides a different cell type to focus on for immunosuppression, with the idea of inhibiting host antigen presentation and stopping the process of immune stimulation right at the beginning."
The lead author on the report is Warren D. Shlomchik. The other Penn-based authors are Matthew S. Couzens and Cheng Bi Tang. The coauthors affiliated with Yale University are Jennifer McNiff, Marie E. Robert, Jinli Liu, and Mark J. Shlomchik.
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