Bone marrow transplantation is not always fully successful because of host versus graft responses (Hybrid resistance) and graft versus hot disease (GVHD). The role of interferon (IFN) in these problems is unclear. In vitro models of GVHD and hybrid resistance using bone marrow cells should greatly enhance our understanding of these problems. I have demonstrated that murine bone marrow cells stimulated with alloantigen produce high levels of IFN (Alpha/Beta). This IFN production was regulated by bone marrow T cells and could be induced by soluble factors produced by activated T cells. Using this in vitro culture system, IFN production also appeared to correlate with in vivo hybrid resistance.
The aim of this proposal is to investigate the cellular interactions involved in the production of IFN by alloantigen stimulated bone marrow cells and to investigate the role of IFN in GVHD and hybrid resistance. The reactive cells involved in these responses will be characterized according to size, density, presence of Fc receptors, adherence properties, and for surface antigens associated with different cell types. Different soluble factors produced by activated T cells will be evaluated for their ability to induce IFN production. These soluble factors will include T cell growth factor (IL 2), colony stimulating factor (CSF), macrophage cytotoxic factor (MCF), and macrophage activation factor (MAF). Other experiments will determine whether in vitro production of IFN by parental and/or F1 bone marrow cells correlates with the in vivo hybrid resistance, and whether this represents a unique in vitro model for hybrid resistance. The in vivo role of IFN in GVHD and hybrid resistance will also be investigated. The types (Alpha/Beta or Gamma) and levels of IFN will be determined in the sera of mice either undergoing GVHD or rejecting parental bone marrow cells (hybrid resistance). Experiments will also document whether or not GVHD, hybrid resistance, and/or serum IFN are affected by depleting donor marrow of cells that are necessary for IFN production in vitro. Results from these studies will not only contribute significantly to our basic understanding of bone marrow cells, but will also provide the information necessary for establishing in vitro models of GVHD and hybrid resistance using bone marrow cells.
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