HUMAN-MILK PROTEINS INCLUDING SECRETORY IGA FAIL TO ELICIT TOLERANCE AFTER FEEDING

Oral administration of large doses of protein antigen generally induce s a state of systemic unresponsiveness currently termed mucosally indu ced tolerance. In this study, we used human milk protein (HMP) without casein as a multi-protein antigen for the study of mucosally induced tolerance. The HMP utilized in this study mainly contained secretory ( S) IgA, lactoferrin (Lf) and alpha-lactalbumin (Lact), When mice were given 1 or 25 mg of HMP orally 3 times or 25 mg orally four consecutiv e weeks prior to systemic immunization, antigen-specific serum IgG res ponses to HMP were induced by subsequent parenteral immunization with 100 mu g of HMP. Analysis of IgG subclasses revealed that IgG1 followe d by IgG2b accounted for the IgG responses noted. When both HMP and ov albumin (OVA) were fed to mice, tolerance developed to OVA but not to HMP. To further investigate the nature of immune responses seen follow ing oral gavage of HMP, we examined responses to individual protein of HMP. Brisk serum IgG1 and IgG2b responses to both S-IgA and if were i nduced by oral followed by systemic immunization with HMP. Analysis of splenic CD4(+) T cells from mice given oral HMP revealed production o f T(h)2- but not T(h)1-type cytokines. These results show that oral ad ministration of HMP preferentially induces exclusive T(h)2-type immune responses, which may prevent the development of HMP (S-IgA and Lf)-sp ecific mucosally induced tolerance.