Antigen-specific modulation of graft-versus-host reactions by two distinct placental factors.

We have previously shown that two distinct mouse placental fractions (PF) are potent immunomodulators in vivo. A 40 kDa PF induces a marked decrease of plaque forming cell (PFC) responses, while a 60 kDa PF increases them. Both effects are specific for the priming antigen. In the present study, these two PF are assayed on a cell-mediated response to allogeneic cells, i.e. in a local graft-versus-host reaction (LGVHR). Mice were primed with allogeneic cells in the presence of various amounts of the 40 kDa or 60 kDa PF, or liver extract (LE) as control. Six days later, their spleen cells were injected into the footpads of F1 recipients. Precise dose-response curves were established and the kinetics of the GVH response were carefully followed. Parallel with the modulation of PFC responses, the 40 kDa PF caused a potent inhibition of the LGVHR, while the 60 kDa PF greatly enhanced it. Both effects were specific for the alloantigens injected with the PF. Furthermore, we showed that these modulations were observed whatever the intensity of the GVH reaction, which varied according to the number of primed spleen cells transferred. This report also demonstrates that these PF can be greatly enriched by passage over affinity columns made of insolubilized lectins. The 40 kDa PF is retained on and can be eluted from columns of insolubilized concanavalin A (Con A) or wheat germ agglutinin (WGA), which indicates that it is a glycoprotein. Conversely, the 60 kDa PF does not bind to any of the above lectins and is probably not a glycoprotein. This biochemical purification step is also a good procedure for obtaining an even cleaner separation of the two fractions from each other. Thus, this paper demonstrates that both PF have important regulatory properties on specific cellular immune responses.