Mechanism Uncovered That May Explain How The Mother Tolerates The Fetus

Immunologically speaking, pregnancy is a strange condition for the mother. The fetus is made up of maternal and paternal proteins. Under normal circumstances, the mother would reject the paternal antigens, and therefore also the fetus, as being foreign, just as she would with any other transplanted body: a kidney or a heart, for example. To prevent rejection of organ transplants, the immune system must be suppressed. In the same way, a successful pregnancy depends on natural processes that suppress the maternal immune response to the fetus during gestation. In the January issue of Nature Immunology (Vol. 2, Issue 1, 01 Jan 2001), researchers from Georgia and Missouri, USA, have shed light on a mechanism that may explain how the mother tolerates the fetus.

Scientists know that, in the mouse, an enzyme called IDO is present in the uterus; it protects fetuses from destruction by maternal T cells. They also know that inhibiting IDO results in the loss of that protection and the consequent rejection of the fetus. Dr. Andrew Mellor and colleagues wondered how IDO induces tolerance. They analyzed pregnant female mice treated with the IDO inhibitor to investigate what happens when fetuses that contained paternal proteins are rejected. They found that T cells caused the deposition, at the maternal-fetal interface, of immune molecules that circulate in the blood (which are collectively known as complement) and of other molecules associated with inflammation. These proteins destroy the interface and are a likely cause for the loss of fetal viability.

This new work furthers our understanding of how the immune system is controlled during pregnancy. If it turns out that some cases of recurrent spontaneous abortions in humans are due to insufficient IDO, perhaps increasing IDO would help the mother to tolerate the fetus. In addition, this information could be potentially useful to the field of transplantation; perhaps we will be able to exploit the abilities of IDO to suppress immunity when appropriate.

CONTACT:

Andrew L. Mellor
Medical College of Georgia
Program in Molecular Immunology
Institute of Molecular Medicine and Genetics
1120 15th Street
CA 2006
Augusta, GA 30912-2600
Tel: 706-721-8735
Fax: 706-721-8732
mellor@immag.mcg.edu

(C) Nature Immunology press release.

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