Effect of organ culture on the survival of thyroid allografts in mice.

Mouse thyroid can be maintained in organ culture for 4 weeks. Uncultured BALB/c thyroid is rejected 10-15 days after transplantation under the kidney capsule of H-2 disparate recipients (C57BL, CBA). Organ culture of thyroid tissue prior to transplantation prolongs allograft survival. This prolongation of graft survival increases with increasing time in culture and 80-90% of BALB/c thyroids maintained in culture for 26 days survive in allogeneic CBA recipients for a 60- to 70-day test period. These allografts show normal function as measured by 125I uptake, and show no histological evidence of chronic rejection. Cultured allografts can be rejected if the host's immune system is stimulated with viable leukocytes of donor origin. Host animals carrying a functioning allograft are not tolerant of donor tissues and will reject a second uncultured allograft from the same donor strain.

Human synovial fibroblast plasminogen activator. Modulation of enzyme activity by antiinflammatory steroids.

Human synovial fibroblasts in culture have been shown to have low plasminogen activator (PA) activity; however, conditioned medium from concanavalin A-stimulated peripheral blood mononuclear cells (c-MCCM) stimulates the cellular levels of this protease. The present study shows that low concentrations of a series of antiinflammatory steroids inhibit the PA activities of both unstimulated and c-MCCM-stimulated fibroblasts. Dexamethasone, the corticosteroid studied in greatest detail, suppresses both the extracellular and cell-associated enzyme activities; this inhibition is rapid, reversible, and is not due to the inhibition of cellular RNA, protein, or DNA synthesis. PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation. These in vitro observations suggest that physiologic and/or pharmacologic control of the PA levels in synovial fibroblasts might also be achieved in vivo by the interacting effects of mutually antagonistic agents, namely, a product from stimulated mononuclear cells and glucocorticoids.

Mechanism of thyroid allograft rejection.

Balb/c thyroids, held in organ culture for 26 days, survive and function as well as isografts for greater than 100 days in CBA recipients. Uncultured allografts are totally rejected by 20 days after transplantation. Prolonged allograft survival can also be achieved by the treatment of donor animals with cyclophosphamide prior to harvesting tissues for transplantation. These allografts do not survive as well as 26 day cultured allografts, but cyclophosphamide pretreatment reduces the culture time required to achieve indefinite survival to 7 days. The provision of an allogeneic (LD) stimulus by thyroid tissue that is I-region incompatible with the host does not facilitate the rejection of a tolerated cultured allograft. However, activation of the host immune system by an uncultured graft syngeneic to a tolerated cultured allograft leads to the chronic rejection of the cultured transplant. The transfer of a tolerated cultured allograft back to its strain of origin induces an acute inflammatory reaction that causes tissue damage within the transplant but does not lead to the total destruction of the tissue.