Our immune systems are designed to respond to dangerous intruders. While the obvious laundry list of bad guys consists of pathogenic viruses and bacteria, there are several other inhabitants that exist within an immunological gray area. Cancerous cells, for example, are not foreign. They’re just badly-behaved versions of our own cells. While it is known that the immune system frequently disciplines cells with cancer pipe dreams by killing them, the existence of malignant disease shows that sometimes the selfish cells get their way.

On the other side of the coin, consider the developing fetus, which contains DNA from both mother and father, and is therefore partially foreign to the mother’s immune system. Unlike cancer – a mischievous self – the fetus is a precious foreign inhabitant that must be nurtured rather than eliminated. In a study recently published in Nature, researchers led by Jared H. Rowe, PhD, at the University of Minnesota, illuminate the mechanisms that the immune system employs to shelter the fetus from attack.

Although T cells are best known for their seminal role in sniffing out foreign invaders and killing them, some T cells are immunological wet blankets instead. T regulatory cells (Tregs) dampen immune responses to harmless inhabitants, and are known to play a key role in protecting the developing fetus from attacks waged by their killer T cell cousins. Rowe’s study moves this story a step further by showing that, in a pregnant mouse model, this protective population of Tregs specifically recognizes paternal proteins expressed by the fetus. Following birth, these fetus-shielding Tregs stick around, lying in wait for the next pregnancy, when they perform their wet-blanketing duties with even more gusto than the first time around. If the father is different for the second pregnancy, then new Tregs need to be called to the job instead.

The study, which is the first to reveal fetal-specific “memory Tregs” that endure after the first pregnancy, could offer clues about the causes of preeclampsia, a syndrome which can lead to miscarriage. Preeclampsia is characterized by insufficient tolerance to the fetus, and it occurs with much higher frequency during first pregnancies or when the father is different in a subsequent pregnancy. Increased protection afforded by memory Tregs could therefore explain why second pregnancies with the same father are at lower risk for pre-eclampsia. The new data may also shed light on autoimmune disorders and point to novel therapies that promote the expansion of these party-poopers with a good memory.

Previously: Why some autoimmune diseases go into remission during pregnancy
Photo by Thomas van Ardenne

Jessica Shugart, a science writing intern with a PhD in immunology, is a graduate student in the Science Communication Program at UC Santa Cruz.