The fetus, and its placenta, is effectively a foreign tissue graft, since half of the fetal genome is paternal, but how the fetus/placenta avoids rejection by the maternal immune system is not clear. One possibility is that placental extracellular vesicles (EVs) induce maternal immune tolerance. In vitro, placental EVs are reported to interact with a range of leukocytes1,2. However, placental EVs in injected into mice were unexpectedly absent from the spleen suggesting that the in vitro interactions were not replicated in vivo3. Here we explore this discrepancy.
CMTPX-labelled MVs were obtained from placental explants. Matched quantities of MVs from the same placenta were; 1) incubated in vitro for 30 minutes with leukocytes, obtained following red blood cell lysis of whole blood, or 2) injected via a tail vein into CD-1 mice (N=5). Leukocytes were obtained from the mice following cardiac puncture, 30 minutes after injection. The interaction of MVs with leukocytes was examined by FACs.
Following in vitro incubation, a large number of leukocytes interacted with the MVs. However, far fewer leucocytes interacted with the MVs in vivo. Two of the mice showed little or no interaction of injected MVs with leukocytes while the remaining three mice showed limited interactions between MVs and leukocytes.
Our results demonstrate that the extent of interactions between placental MVs and leukocytes in vitro differs substantially from the number of interactions that occur in vivo. This raises the caveat that care must be taken when extrapolating in vitro experiments to the in vivo situation.