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 β-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 β-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 β-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.