Tiny Invader

Monday, February 01, 1999
How does a fetus manage to survive inside its mother's womb without being attacked and rejected by her immune system? After all, to the mother's immune system a fetus is no different from, say, a skin graft or a kidney transplant--it's foreign tissue, composed of cells derived in part from the father. It turns out that the fetus has a relatively straightforward means of defense. Researchers have found that the fetus produces an enzyme that starves the mother's immune system cells of an essential nutrient.

About two years ago, oncologist David Munn of the Medical College of Georgia discovered that macrophages, a type of immune cell, can paralyze killer T cells, which attack foreign tissue. Macrophages accomplish this by producing an enzyme called IDO, which destroys the amino acid tryptophan, one of the building blocks of proteins. Without tryptophan, T cells can't divide and reproduce, and the immune response is hamstrung.

Other researchers had detected IDO in the placenta, the interface between mother and fetus, which led Munn to wonder if the fetus might use IDO to turn off the mother's T cells by starving them of tryptophan. If so, then blocking the production of IDO in the placenta should cause the mother to reject the fetus.

Munn, with immunologists Andrew Mellor and Simon Conway, also of the Medical College of Georgia, decided to test the new theory on mice. When a female mouse and her fetus were genetically different, as is invariably the case in any normal pregnancy because of the genes contributed by the sperm, a chemical that neutralized IDO caused the mothers to abort their embryos. However, in genetically identical inbred mouse strains--descended from generations of parents of identical twins--and in pregnant mice without working immune systems, the IDO blocker showed no effect. "What's attractive about this theory," says Mellor, "is that nobody has ever considered the mechanisms we've come up with." He also suspects that the fetus's strategy of starving the immune system might lead to new approaches to treating diseases such as rheumatoid arthritis, where the immune system attacks the body's own tissues. "There might be a role for IDO in putting the brakes on T cell responses to keep us free of autoimmune diseases."
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