In some people, the immune system has a disconcerting tendency to revolt: For some reason, it viciously attacks the body itself. For years scientists have wondered what triggers this rebellion. Now, a team of immunologists may have hit on an important piece of the puzzle: an aggressive overproduction of a class of T cell that attacks the body's tissues. This T cell coup can be prevented, they found, by exposing the mice to bacteria early in life.
The immune system is like a mini-ecosystem--if there's a shortage of one type of cell, another will furiously multiply to fill the niche. To investigate how this might contribute to disease, immunologists Nora Sarvetnick, Cecile King, and their colleagues at the Scripps Research Institute in La Jolla, California, studied mice predisposed to type 1 diabetes and other autoimmune disorders. By a few weeks of age, before falling sick, these animals had about half the normal number of so-called memory T cells. The cells recall encounters with intruders and defend against future ones.Not surprisingly, Sarvetnick's team found that other T cells were filling the gap the memory cells left behind. What was particularly striking was that these replacements were so-called CD4+ and CD8+ cells, the same ones that go haywire and destroy the pancreas, triggering type 1 diabetes. The rapidly proliferating cells, they found, also sported a specific cell-signaling molecule. Although that marker, called IL21, had not previously been associated with autoimmune diseases, the gene that produces it sits right in the stretch of DNA known to make these mice vulnerable to diabetes, suggesting that IL21 might make a drug target, says Sarvetnick.Furthermore, by giving the animals a shot of dead bacteria--similar to an immunization in humans--when they were newborns, Sarvetnick and her colleagues prevented a surfeit of CD4+ and CD8+ cells. And the animals never got sick, they report in the 16 April issue of Cell. The approach lends credence to the so-called "hygiene hypothesis," which argues that exposure to toxins early in life--in the case of the mice, the inoculated bacteria--helps prevent allergies and autoimmune diseases.The finding provides some evidence to support a link between a low T cell count and autoimmune diseases, although it's still not clear that one exists, says Michael Bevan, an immunologist at the University of Washington, Seattle. Sarvetnick now hopes to collect some human samples from patients to see whether her theory holds up there.