关键词:
Antigens, CD34/immunology
Bone Marrow Cells/drug effects*
Bone Marrow Cells/immunology*
Bone Marrow Transplantation/immunology*
Cadaver
Cell Differentiation/physiology
Cell Division/physiology
Humans
Immunity, Cellular/drug effects
Immunity, Cellular/immunology
Immunosuppressive Agents/pharmacology*
Lymphocyte Activation/drug effects
Lymphocyte Activation/drug effects
Lymphocyte Activation/immunology
Lymphocyte Activation/immunology
Tissue Donors
T-Lymphocytes/immunology
摘要:
Background. The cascade of immunological effects brought about by donor bone marrow cell (DBMC) infusions in human organ transplantation, especially in the context of continuous pharmacologic immunosuppression, is not fully understood. Yet, in inbred rodents and even primates, administration of specific bone marrow cells has caused a state of acquired immunologic tolerance. Methods. In vitro mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) culture systems were used to compare the responding and regulatory properties of DBMC and individual bone marrow cell subsets versus spleen cells in the presence or absence of pharmacologic immunosuppression. Results. In the absence of immunosuppressive drugs, the DBMC proliferated in MLC and in response to phytohemagglutinin, but to a lower magnitude than donor spleen cells. In CML assays, DBMC failed to function as cytotoxic cells. Removal of both CD3(+) and CD34(+) cells together (not just singly) had to occur for complete abrogation of the proliferative response of DBMC evoked in the presence of allogeneic stimulating cells. Testing several experimental variables using flow cytometric analysis led to the conclusion that when purified DBMC CD34(+) cells were placed in coculture with irradiated allogeneic peripheral blood mononuclear cells, such CD34(+) cells give rise both to CD3(-) TCR alpha beta(+) as well as to dimly staining CD3(+) TCR alpha beta(+) cells. Low pharmacologic concentrations of tacrolimus/cyclosporine (CsA) and mycophenolic acid (MPA) singly or in combination had no effect on the spontaneous proliferation of DBMC and had significantly less inhibitory activity on MLC responses of DBMC and its purified CD3(+) or CD34(+) subpopulations, compared with the responses of spleen cells. Moreover, the previously described regulatory effects of DBMC on the MLC responses of peripheral blood or splenic responding cells were not inhibited by these immunosuppressive drugs. Conclusions. Taken together, these