Why doesn't the body reject the fetus?

Researchers from the National Cancer Institute have isolated a compound from the urine of pregnant women that has immunosuppressive capabilities. The compound, which the Bethesda, Md., scientists have named uromodulin, may play a role in preventing rejection of the placenta and fetus.

Because half of the placenta's genetic makeup comes from the father, the placenta is, in effect, a graft. Yet the mother's system does not reject the placenta as it would a transplanted lung or kidney. This "graft acceptance" has evaded scientific explanation.

That's not for lack of suggestions. Various biochemicals isolated from the urine of pregnant women have been put forth as immunosuppressives that could inhibit the mother's rejection response. But none has stood the test of time.

To isolate their immunosuppressive candidate, Andrew V. Muchmore and co-worker Jean M. Decker started with urine from pregnant women and ran it through an exacting series of steps that separated the compound based on its characteristic size and biochemistry. They identified the compound in each step by measuring the ability of various fractions to inhibit the proliferation of immune cells stimulated with tetanus toxoid.

Having isolated the compound, a feat they detail in the Aug. 2 SCIENCE, the researchers' next step is to determine exactly what it does during pregnancy and in the normal regulation of the immune response. "We're not willing to say uromodulin is [totally] responsible for the maintenance of the placenta," says Muchmore. "How the placenta is protected is an open question. But uromodulin is much more active than any other factor isolated from pregnant women's urine."

Muchmore and Decker have found that when certain white cells are isolated and grown in culture, uromodulin inhibits their activity only when added at the beginning of the culture. This suggests that it interferes with an early stage of the immune system process. If the immu nosuppressive capability holds up under further inspection, uromodulin could join such recently discovered immune system modulators as interleukin-1 and 2, interferon and tumor necrosis factor, all of which are just now being placed on the scientific map. "Uromodulin is intrinsically interesting as an immunosuppressive compound even if it turns out to play no role in pregnancy," Muchmore says."