Too old to help

Autoreactive T cells are harmless until they are prodded into action by exposure to common microbes, according to Yoshitomi and colleagues on page 949. These results may help explain the contribution of environmental factors to human autoimmune diseases like rheumatoid arthritis and diabetes. While studying an arthritis-prone strain of mouse, Yoshitomi et al. noted that these mice did not develop disease when housed in a microbe-free environment, despite the presence of T cells that could induce arthritis when transferred to nude mice. Only when mice were moved to nonsterile conditions (where they acquired fungal infections) or were injected with -glucans from fungal cell walls did the telltale symptoms of arthritis appear. Treatment of the mice with antifungal drugs or antibodies that blocked binding of -glucans to cells reversed this effect, suggesting a direct link between exposure to fungi and development of disease. The same fungal products that triggered arthritis stimulated dendritic cells (DCs), the cells responsible for activating T cells, to upregulate costimulatory molecules and secrete cytokines. The authors suspect that -glucans, detectable in the circulation during infection, reach the local lymph nodes where they prompt DCs to activate autoreactive T cells. Once activated, the T cells invade the joints. The group now plans to investigate possible defects in regulatory T cells in this model, as these cells normally keep autoreactive T cells in check.