Purification of placenta-eluted gamma globulins and their strong effect against graft-versus-host reactions in vitro and in vivo.

In the 1980s, attempts were made to use placenta-eluted gamma globulins (PEGG) in patients with graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). Because production of PEGG had been discontinued for many years, we aimed to reestablish a method of production and further explore the mechanisms of the effect of these globulins on GVHD. PEGG were prepared by elution at acid pH from extensively washed human placenta followed by precipitation with saturated ammonium sulfate and absorption on a protein A Sepharose column. In vitro study showed PEGG significantly inhibited both the proliferative response of T-cells to phytohemagglutinin (PHA) and the mixed lymphocyte reaction (MLR). Results of flow cytometric analysis indicated that PEGG down-regulated the expression of CD25 and CD69 on T-cells stimulated by PHA. Cytokine quantification in MLR supernatant showed that PEGG decreased secretion of interferon 3 (IFN-3) but increased production of interleukin 4. In a murine GVHD model, we investigated the preventive effect of PEGG on lethal GVHD in irradiated recipients of allogeneic bone marrow cells and spleen cell transplants by in vivo administration. Compared with controls, recipients treated with PEGG had a markedly increased survival rate with less histopathological evidence of GVHD. These results suggest that PEGG may be a potent therapeutic agent for GVHD.