Research Explores Recurrent Miscarriages, Hoping to Help Transplant and Cancer Patients.

2001 JAN 18 -- (NewsRx.com) -- A mother's immune system may attack a fetus from multiple fronts, by sending in killer T cells, by producing antibodies that target fetal cells, or by coating cells with a destructive, soluble blood factor called complement, according to researchers at the Medical College of Georgia.

The grim attack described by researchers may surprise immunologists who would expect the T-cell attack, but not complement, the lethal component of an immune response that more typically would attack invaders such as viruses and bacteria coated by antibodies made by B cells.

"We now know that the nature of the attack is somewhat different than we had assumed," said Dr. Andrew L. Mellor, immunologist and chief of the MCG Program in Molecular Immunology. "We assumed that the maternal T cells would get activated by fetal antigens, expand in number, then start to kill fetal cells and we cannot exclude that at this point."

But in research published in the January 2001 issue of Nature Immunology, they also found deposits of complement -- a component of the innate immune system which neutralizes foreign objects such as invading bacteria or virus coated by antibodies. In a normal immune response, T cells come in to attack and destroy viral-infected cells while antibodies and complement attack bacteria and viruses still floating around in the bloodstream. Antibodies coat viral cells, activating the complement deposition and eventually killing the virus.

"What has not been resolved by our research is the connection between activating the maternal immune response and, as an end point, depositing complement," Mellor said. "The broad assumption has been that there is not a connection between T cells and complement."

To further explore new evidence that there may be, the MCG researchers already are looking at a model that has a factor produced by T cells which may activate the complement. They say the increased understanding of the maternal immune system's response has implications for better understanding recurrent misearriages as well as for development of drugs which can manipulate the localized response to help a transplant patient keep his new organ and to help a cancer patient "reject" his tumor.

The MCG research team, led by Mellor and Dr. David Munn, described in the August 1998 edition of Science a mechanism for localized suppression of the mother's immune system that enables the fetus to escape attack. They found that during pregnancy, ...