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Reversal of Orally Induced T‐Cell Tolerance by Subcutaneous Administration of Interleukin‐12 at the Site of Attempted Sensitization
Author(s) -
SCHEPER RIK J.,
BLOMBERG B. MARY E.von,
GROOT JAN de,
WOLVERS DANIELLE A. E.,
KRAAL GEORG,
CLAESSEN ANKE M. E.
Publication year - 1996
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1996.tb52706.x
Subject(s) - ovalbumin , sensitization , immunology , immune tolerance , route of administration , immunoglobulin e , interleukin 4 , immunization , medicine , antibody , cytokine , immune system
Feeding of proteins causes peripheral T-cell tolerance, as revealed by reduced delayed-type hypersensitivity (DTH) reactivity after immunization. Using ovalbumin-fed mice, we studied whether putatively immunostimulatory cytokines could reverse this state of mucosal tolerance. It was found that local administration of neither IL-2, IFN-gamma, nor GM-CSF resulted in reversal of tolerance. In contrast, subcutaneous administration of IL-12 at the site of attempted immunization resulted in complete recovery of DTH reactivity. The dichotomy between the two Th1-stimulatory cytokines IFN-gamma and IL-12 was also reflected by different effects on ovalbumin-specific antibody isotypes. Although both IFN-gamma and IL-12 downregulated serum IgG1-levels in tolerant mice, suggesting decreased ovalbumin-specific Th2 function, only local administration of IL-12 led to increased serum Th1-related IgG2a levels. These results support the view that potentiation of Th1 effector function is critical for reversal of mucosal tolerance.