Mechanisms of immune tolerance to food antigens in humans

Immune responses and the mechanisms of tolerance to the common dietary anti gens bovine gamma globulin (BGG), ovalbumin (OVA), and soybean protein were evaluated in normal human volunteers. Humoral and T cell proliferative res ponses to these antigens were measurable but low, consistent with immune to lerance. There were limited correlations between responses in the systemic and mucosal compartments, and in general the responses to one dietary antig en could not predict the response to another. T cell proliferation to dieta ry antigens increased significantly by addition of recombinant human interl eukin-2 (rhuIL-2). Peripheral blood mononuclear cells stimulated with BGG o r OVA expressed IEL-Ma chain but not IL-2 mRNA, consistent with T cell aner gy. Incubation with exogenous IL-2 alone did not restore T cell proliferati on to BGG or OVA. In some individuals T cell proliferation to an un elated vaccine antigen was suppressed by addition of BGG or OVA, but could be reve rsed with low doses of rhuIL-2. We conclude that in humans anergy is the ma jor mechanism of tolerance to chronic antigen feeding, and we propose that such anergic, antigen-specific T cells actively contribute to maintenance o f homeostasis in the intestine in the face of massive antigen challenge. (C ) 2001 Academic Press.