A molecule expressed in the earliest stages of pregnancy that vanishes when the baby is born seems to keep some cells responsible for directing the immune system in an immature and accepting stage, Medical College of Georgia researchers says.
Their finding that the molecule HLA-G helps make dendritic cells - which work like air-traffic controllers for the immune system - tolerant helps explain how a fetus, with genes from both parents, can avoid rejection by the mother's immune system.
And it has them optimistic that the natural mechanism could be replicated to help preserve a transplanted heart or kidney.
'These immature dendritic cells can induce suppressor cells that will suppress the immune response,' said Dr. Anatolij Horuzsko, reproductive immunologist.
He is principal investigator on a $ 1.3 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to explore whether this selective immune suppression - which occurs in the placenta where mother and developing baby touch - can help transplant patients avoid rejection without putting them at risk for new infection and disease.
Dr. Horuzsko and his co-investigator Dr. Oscar H. Grandas, transplant surgeon, say it's a logical pursuit because a fetus is essentially a transplant in which, for nine months, a developing body containing genetically foreign material - the half he gets from his father - often escapes rejection by the mother's immune system.
It's believed that some lost pregnancies result when, for some reason, localized suppression doesn't happen.
Amazingly there is evidence that in some transplant patients natural suppression also occurs.
Some of the many questions Drs. Horuzsko and Grandas want to answer are, 'Is the spontaneous suppression mechanism that occurs in some patients the same one that occurs during pregnancy?' and 'Can they make the suppression happen for all patients?'
Dr. Horuzsko has found that HLA-G binds with the inhibitory receptor on the surface of dendritic cells, leaving the cells, at least for a time, immature and tolerant.
In research, published in 2002 in the European Journal of Immunology, he performed skin grafts on transgenic mice which express HLA-G and found some of the dendritic cells oddly changed and nonresponsive, a state which enabled the skin grafts to survive about a month longer than those on normal mice. The human equivalent likely would be much longer since a day in a mouse's life translates to about a month for a human.
This mechanism provides a targeted escape from the usual rigorous patrol of the immune system. HLA-G is an antigen, which is a substance that gets the attention of the immune system; good antigen matches are desirable between an organ donor and transplant recipient because it reduces the risk of rejection.
Source: medicalnewstoday.com
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