Regulatory T cell receptor genes vary by location.

On page 3105, Lathrop et al. show that different organs carry different combinations of the T cells that forestall autoimmune attacks. The study is the first to demonstrate that the immune system customizes its measures for preventing autoimmunity.

Regulatory T (T reg) cells curtail autoimmunity by stifling assaults from activated T cells. After maturing in the thymus, T reg cells disperse throughout the body. Indirect evidence hints that the immune system adjusts the T reg cell lineup in each organ to match that organ's unique antigen profile. So the liver would harbor more T reg cells that prevent attacks on liver antigens, whereas the stomach would preferentially house those that shelter distinctive stomach proteins. However, researchers hadn't yet shown this immune tuning.

Lathrop et al. gathered T reg cells from the spleen and lymph nodes of mice. The team then sequenced the genes encoding the T cell receptor (TCR), which determines what antigen the cell targets. As the researchers suspected, T reg cells from different locations tended to have different TCRs. The T reg cell population in the lymph nodes draining the intestines was distinct from that of the nodes in the neck and that of the spleen. By contrast, populations of naïve T cells didn't vary from place to place.

One possible explanation for the local differences is that exposure to a particular antigen causes naive T cells to transform into T reg cells—what's called conversion. To gauge the importance of conversion, the researchers transferred labeled naïve and memory T cells into the mice and determined how many settled down in the spleen and lymph nodes and became T reg cells. The results indicated that conversion furnished only about 4–7% of the overall T reg cells. What might happen instead, the team suspects, is that an assortment of T reg cells arrives in an organ from the thymus, but only those that encounter an antigen they recognize multiply.