Mechanisms of immune tolerance relevant to food allergy

The intestine has an unenviable task: to identify and respond to a constant barrage of environmental stimuli that can be both dangerous and beneficial. The proper execution of this task is central to the homeostasis of the host, and as a result, the gastrointestinal tract contains more lymphocytes than any other tissue compartment in the body, as well as unique antigen-presenting cells with specialized functions. When antigen is initially encountered through the gut, this system generates a robust T cell-mediated hyporesponsiveness called oral tolerance. Although seminal observations of oral tolerance were made a century ago, the relevant mechanisms are only beginning to be unraveled with the use of modern investigational techniques. Food allergy is among the clinical disorders that occur from a failure of this system, and therapies that seek to re-establish tolerance are currently under investigation. (J Allergy Clin Immunol 2011;127:576-84.)