Reversal of orally induced T-cell tolerance by subcutaneous administration of interleukin-12 at the site of attempted sensitization.
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.
Scheper
R J
RJ
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
von Blomberg
M E
ME
de Groot
J
J
Wolvers
D A
DA
Kraal
G
G
Claessen
A M
AM
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000276:immunology; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage; D018664:Interleukin-12 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin