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Mom's Cells Prime Fetal Immune System
Date:12/4/2008

Process prevents growing baby from rejecting the mother, researchers find

THURSDAY, Dec. 4 (HealthDay News) -- During pregnancy, many of the mother's cells enter the fetus and produce immune cells that prevent the growing baby from rejecting its mother, new research shows.

This finding shows that the two coexist by making the fetus' immune system able to tolerate foreign antigens and could lead to new techniques in stem cell treatments and ways to deal with chronic infections, researchers say.

"The fetal immune system may be considerably more active than previously thought, and a better understanding of fetal immunity may help us to better understand a range of health concerns including fetal infections and autoimmunity," said lead researcher Jeff Mold, a graduate student in the Division of Experimental Medicine at the University of California, San Francisco.

"The findings also suggest that the fetal immune system may be a good target for vaccination strategies aimed at promoting immunological tolerance in human beings," he said.

Modifying the immune system could be important in treating autoimmune diseases, in which the body attacks its own cells, and in preventing organ transplant rejection, where the body rejects the transplanted tissue, the researchers noted.

In addition, the finding may also be important in developing treatments for infectious diseases such as HIV.

"Only 5 to 10 percent of babies born to untreated HIV-infected mothers in the absence of antiretroviral interventions are born infected with HIV. Perhaps some aspect of the immunological tolerance of the fetal immune system explains how the baby could avoid HIV infection in utero," study co-author Dr. Joseph M. McCune, head of the Division of Experimental Medicine, said in a statement.

This study opens up new avenues of research that could be important in developing effective HIV vaccines, McCune noted.

The report was published in the Dec. 5 issue of Science.

In experiments with human tissue, the researchers found that maternal cells were present in the developing fetal lymphoid tissues early in pregnancy when the fetal immune system is first developing, Mold said.

"In addition, we found that the fetal immune system contains a large population of regulatory T-cells (Treg), which blocked fetal T-cell responses to maternal cells," Mold said.

Mold's team also showed that when fetal T-cells were stimulated with cells from an unrelated donor, they became regulatory T-cells. These newly developed Treg were able to suppress fetal T-cell responses against this donor.

"Finally, we showed some evidence that Tregs in the blood of children 7 to 17 [years old] were more effective in blocking T-cell responses to maternal cells than they were to paternal cells," Mold said.

The human fetal immune system may play a specific role in mediating immune tolerance to both self and foreign antigens encountered during fetal development, Mold said.

"Little is currently known about the fetal adaptive immune system and the functional properties of fetal T-cells," Mold said. "These are current areas of investigation in the lab. This paper represents a first step in trying to understand the role of the fetal adaptive immune system but much more is needed to be done," he added.

Dr. Rachel L. Miller, an associate professor of medicine and environmental health sciences at New York Presbyterian Hospital/Columbia University Medical Center in New York City, thinks the finding dispels that myth that the fetal immune system is not well-developed.

"The paper demonstrates beautifully that the fetal adaptive immune system is competent and functional enough to establish tolerance when needed," Miller said. "This work provides another example about how sophisticated the fetal immune system can be."

Sandra L. Nehlsen-Cannarella, director of Immunogenetics at Detroit Medical Center and an expert in fetal immunity, agreed that the infant immune system is actually well-developed.

"Their immune system is quite capable of doing things," Nehlsen-Cannarella said.

Nehlsen-Cannarella noted the study confirms what is seen in clinical practice. "This is a great verification of what many of us have already believed," she said. "This forms a basis to do what we have all been looking for; to induce tolerance for transplantation as well as protecting the infant against infections in its future."

More information

For more about the immune system, visit the U.S. National Institute of Allergy and Infectious Diseases.



SOURCES: Jeff Mold, graduate student, Division of Experimental Medicine, University of California, San Francisco; Rachel L. Miller, M.D., associate professor, medicine and environmental health sciences, New York Presbyterian Hospital/Columbia University Medical Center, New York City; Sandra L. Nehlsen-Cannarella, Ph.D., director, Immunogenetics, Detroit Medical Center; Dec. 5, 2008, Science


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