Regulatory T cells, which function like immune system police, learn early in life what to protect, and that may include viruses, bacteria and tumors, researchers have shown.

All T cells are made in the bone marrow, then move to the thymus where they differentiate, upregulating surface receptors, which are molecules that detect different antigens. It’s a brutal process—95 percent of the cells die in the thymus primarily because they recognize body tissue—that winds down after puberty.

Using genetically manipulated mice and technology that enables a snapshot of the antigen receptors that determine what cells recognize, MCG researchers followed T cells as they moved from the thymus to the rest of the body.

They found that regulatory T cells learn in the thymus what to protect and that some of the information may be faulty, according to research in the August 2006 issue of Immunity.

Unfortunately, the cells may not learn to recognize all endogenous tissue, a limitation that can lead to autoimmune disease.

T cell schooling in the thymus peaks in the first six weeks of life in the mouse, which roughly translates to the first 15 years of human life. Those early lessons seem to last a lifetime, and the few regulatory cells that develop later will be like the early cells, said Dr. Rafal Pacholczyk, MCG immunologist and lead author.

The findings mean that essentially from the beginning, some people may have regulatory T cells less skilled at keeping the immune system from attacking their bodies and/or too skilled at protecting invaders.

The research offers hope that the cells can be manipulated to vaccinate against diseases such as lupus, arthritis and type 1 diabetes. Or more cells might be added to protect those with inadequate police.

“We need some regulatory cells more than others,” said Dr. Ignatowicz. “We probably need more of the ones that recognize autoantigens on the pancreas and [fewer of] the ones that recognize tumors.”

The fact that most regulatory T cells come directly from the thymus, not from other circulating T cells, also was previously unknown. “Where they come from is the main question we wanted to answer,” said Dr. Ignatowicz.

It has been thought that some T cells circulating in the body might make the transformation, possibly because of what they are exposed to in the body. In fact, T cells most aggressive at attacking endogenous tissue likely would be among those converting to protective regulatory cells. “We did not find that does not happen, but it’s not the major mechanism for generating regulatory cells in the body,” Dr. Pacholczyk said.