The human immune system matures in utero much earlier than was previously thought, suggests a paper published online this week in Nature. The finding marks a shift in our understanding of immune system development, and may provide insights into certain pregnancy-related conditions including gestational diabetes and recurrent spontaneous miscarriage.

The developing human fetus is exposed to a wide range of molecules with the potential to activate the immune system, such as microbes and food particles. Florent Ginhoux and colleagues studied tissues from 96 fetuses from the second trimester of pregnancy (ranging from 14 to 22 weeks of gestation), collected from clinically indicated terminations of pregnancies. The authors show that immunologically active cells are present in fetuses as early as the second trimester. These fetal dendritic cells can both sense pathogens and stimulate T cells, indicating they have the potential to initiate an immune response. When exposed to an antigen, however, the cells do the opposite, stimulating the activity of a particular subset of T cells that serve to dampen the immune response.

These results challenge the dogma that the human fetus is unable to mount an immune response, and helps to explain the immune tolerance well known to occur during this time period. The study could also be used to help guide the timing of intra-uterine stem cell transplants, potentially curative treatments for various problems, including immune defects and metabolic disorders.