The mammalian immune system is a complex but impressive product of evolution. It’s able to defend the body against a wide variety of pathogens, and even to some extent against cancer cells. But to do its job most effectively, the cellular agents of the system need to be trained to distinguish their proper targets from other cells in the body that need to be left alone.
Among the cells that need to be left alone are not only all the body’s own cells, which are descendants of a single fertilized egg. There are also about ten times as many bacterial cells in the intestines, which help digest food and cause no problems (as long as they stay in the intestines). But they need to avoid attack from the immune system. How this protection from attack comes about has not been understood. Research just published doesn’t give nearly a complete answer, but does make some significant progress.
The immune system’s primary agents for implementing the system’s policies are T cells. Although there are a number of different types of T cells, they can be sorted roughly into two categories: regulatory T cells and effector T cells. The effector cells are the ones that take action against pathogens that they recognize. The regulatory cells can send signals to the effector cells to temper their activity around cells that need to be protected from the immune system.
Immature T cells originate in bone marrow. Receptors on their surfaces are able to recognize a vast number of protein antigens. These cells are matured in the thymus. T cells which recognize antigens that identify the body’s own cells mature into regulatory T cells. The rest mature into effector T cells.
What the new research has found, in studies on mice, is that regulatory T cells in the intestines also recognize antigens that signify benign intestinal bacteria. Since that could not plausibly have happened in the thymus, it must have occurred in the intestines, where the bacteria are found. But the mechanism behind this is still unknown.
Not all foreign particles in the body warrant destruction, however. Microbes living harmlessly, and often helpfully, in the body evade the immune system’s wrath, but researchers don’t know how. Chyi-Song Hsieh of Washington University School of Medicine in St Louis, Missouri, and his colleagues now report that these microbes seem to provide localized instruction in the gut, telling immature T cells that recognize them to develop into regulatory T cells.
Previous work had suggested that regulatory T cells could be induced outside the thymus, but this is the first demonstration that such peripherally generated cells actually exist.