TY - JOUR

T1 - Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

AU - Kjær, T. M.R.

AU - Frøkiær, H.

PY - 2002

Y1 - 2002

N2 - Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1 ng-1 mg/day) of ovomucoid (OM) for a minimum of 30 days and a maximum of 100 days. It was possible to induce oral tolerance measured as reduced proliferation and antibody production (immunoglobulin (Ig)G1, IgG2a and total Igs) when mice were fed 1 mg of OM/day for 40 or 50 days. It was not possible to induce oral tolerance with daily doses of antigen of 10 μg or less. Feeding of 100 μg OM/day for 40 and 50 days and 1 mg OM/day for 30 days generated tolerization of Th2-dependent responses, but retained an intact response of Th1-dependent antibodies, whereas feeding of 1 mg OM/day for 40 and 50 days resulted in tolerization of both Th1- and Th2-antibody responses. The results presented here suggest that there is a threshold of microgram-doses below which oral tolerance cannot be induced, and that selective suppression of Th2 responses can be achieved by continuous microdose feeding, while an extension of the feeding dose or feeding period tolerizes both Th1- and Th2-dependent responses.

AB - Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1 ng-1 mg/day) of ovomucoid (OM) for a minimum of 30 days and a maximum of 100 days. It was possible to induce oral tolerance measured as reduced proliferation and antibody production (immunoglobulin (Ig)G1, IgG2a and total Igs) when mice were fed 1 mg of OM/day for 40 or 50 days. It was not possible to induce oral tolerance with daily doses of antigen of 10 μg or less. Feeding of 100 μg OM/day for 40 and 50 days and 1 mg OM/day for 30 days generated tolerization of Th2-dependent responses, but retained an intact response of Th1-dependent antibodies, whereas feeding of 1 mg OM/day for 40 and 50 days resulted in tolerization of both Th1- and Th2-antibody responses. The results presented here suggest that there is a threshold of microgram-doses below which oral tolerance cannot be induced, and that selective suppression of Th2 responses can be achieved by continuous microdose feeding, while an extension of the feeding dose or feeding period tolerizes both Th1- and Th2-dependent responses.

UR - http://www.scopus.com/inward/record.url?scp=0036228153&partnerID=8YFLogxK

U2 - 10.1046/j.0300-9475.2002.01076.x

DO - 10.1046/j.0300-9475.2002.01076.x

M3 - Journal article

C2 - 11967117

AN - SCOPUS:0036228153

VL - 55

SP - 359

EP - 365

JO - Scandinavian Journal of Immunology, Supplement

JF - Scandinavian Journal of Immunology, Supplement

SN - 0301-6323

IS - 4

ER -