"The adult immune system's typical role is to see something foreign and to respond by attacking and getting rid of it. The fetal system was thought in the past to fail to 'see' those threats, because it didn't respond to them," said Jeff E. Mold, first author on the paper and a postdoctoral fellow in the McCune laboratory. "What we found is that these fetal immune cells are highly prone to 'seeing' something foreign, but instead of attacking it, they allow the fetus to tolerate it."
The previous studies attributed this tolerance at least in part to the extremely high percentage of "regulatory T cells" those cells that provoke a tolerant response in the fetal immune system. At mid-term, fetuses have roughly three times the frequency of regulatory T cells as newborns or adults, the research found.
The team set out to assess whether fetal immune cells were more likely to become regulatory T cells. They purified so-called nave T cells new cells never exposed to environmental assault from mid-term fetuses and adults, and then exposed them to foreign cells. In a normal adult immune system, that would provoke an immune attack response.
They found that 70 percent of the fetal cells were activated by that exposure, compared to only 10 percent of the adult cells, refuting the notion that fetal cells don't recognize outsiders. But of those cells that responded, twice as many of the fetal cells turned into regulatory T cells, showing that these cells are both more sensitive to stimulation and more likely to respond with tolerance, Mold said.
Researchers then sorted the cells by gene expression, expecting to see similar expression of genes in the two cell groups. In fact, they were vastly different, with thousands of genes diverging from the two cell lines. When
|Contact: Kristen Bole|
University of California - San Francisco