living staves off autoimmunity
Fungal infections trigger arthritis in susceptible SKG mice (arrowheads
indicate fungal spores in the lung).
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 ß-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 ß-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 ß-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.
Heather L. Van Epps