Environmental influences on the development of the immune system: consequences for disease outcome.

Early T cell responses to external antigens and autoantigens are subject to a variety of regulatory mechanisms. A unifying link between the increase in both Th1-dependent autoimmune disease and Th2-linked atopic allergy would be a disturbed immune regulation involving T regulatory cells. There is a strong global correlation between childhood wheezing and diabetes. It is increasingly recognized that microbial colonization of the gastrointestinal tract, linked with lifestyle and/or geographic factors, may be important determinants of the heterogeneity in disease prevalence throughout the world. These suggestions are supported by observations that germ-free mice do not develop tolerance in the absence of a gut flora. The potential effects of environmental stimuli on immune function is greatest in early life including fetal life when systems and responses are developing, and the maternal influences during fetal life could be particularly important for the development of immune regulation and tolerance induction. In recent years, focus has switched from searching for environmental risk factors towards an interest in factors that could induce and maintain immune regulation and tolerance to allergens and autoantigens. Currently evaluated strategies include the use of immunomodulatory factors, such as probiotics, prebiotics, and dietary nutrients, although data are still insufficient to make specific recommendations.