Nature Immunology pp 1123 - 1132 & pp1133 - 1141

Arthritis and allergy are 'two sides of the same coin' as immune responses. Both are caused by overproduction of otherwise important immune molecules. Two papers in the November issue of Nature Immunology describe how one type of immune cell associated with allergic inflammation and autoimmunity ultimately causes disease. This new work clarifies how such cells develop, which may help bring treatment for inflammatory diseases such as asthma and allergy.

CD4 lymphocytes (or 'T helper' cells) are immune 'helper' cells that were formerly thought to function in one of two ways during immune responses. Now, work from the laboratories of Casey Weaver and Chen Dong describe how a novel third type of T helper cell develops. Molecules such as antiviral interferon-gamma (IFN-g) and allergy-associated interleukin 4 (IL-4) are well known to be produced by distinct 'lineages' of T helper cells, whereas distinct molecules have been linked to some T helper cells found in people with autoimmunity. Both Weaver and Dong demonstrate that CD4 T cells can be become producers of interleukin 17 (IL-17), a powerful chemical that stimulates inflammation and has been linked to autoimmunity and allergy. IL-17 is triggered by a unique set of signals that defines this new 'lineage' of CD4 T cells.

This new information may allow treatments for people before they develop symptoms of allergy and autoimmunity instead of only after symptoms occur, which is the basis of the present, less effective treatment.

Nature Immunology pp 1142 - 1151 & pp 1152 - 1159

Autoimmune pathology often occurs because some immune cells are not regulated properly. This important function is usually the responsibility of a special class of cells called regulatory T cells (T_reg cells). A pair of new reports in the November issue of Nature Immunology show that T_reg cells require the immune modulator interleukin 2 (IL-2) for their maintenance and long-term function rather than for development, as previously thought.

How T_reg cells develop has been worked out in some detail and the prevailing model included a fundamental function for IL-2. In fact, for many years, T_reg cells were identified exclusively on the basis of expression of the IL-2 receptor. But the new studies by Alexander Rudensky and Ludger Klein rely instead on identifying T_reg cells by a different molecule, Foxp3.

Using this identifier, both Rudensky and Klein unexpectedly demonstrate that IL-2 signals are not required for T_reg cell development. Instead, IL-2 is required for the maintenance of T_reg cells after they leave the thymus and move into the circulation. This new model for the function of IL-2 will help scientists understand how this critically important class of suppressor cells keeps immunopathology at bay.