Mucosal tolerance is associated with, but independent of, up-regulation Th2 responses.
Intranasal administration of protein antigen is an efficient way to induce mucosal tolerance. Suppressive mechanisms that might be involved in this phenomenon include down-regulation of T-helper type-1 (Th1)-mediated processes by Th2 cells. However, since Th2 responses can also be subjected to mucosal tolerance, we wanted to investigate whether suppression of a typical Th1 response, such as a delayed-type hypersensitivity (DTH) reaction by intranasal tolerance induction, was causally related to up-regulation of Th2 responses. We therefore treated mice either systemically or locally with anti-interleukin-4 (IL-4) or anti-IL-10 antibodies before intranasal tolerance induction or before sensitization for DTH to see whether we could prevent or abrogate tolerance. Although the up-regulation of antigen-specific IgE levels in tolerant mice could be prevented by anti-IL-4 treatment, the extent of tolerance as measured by suppression of DTH was not affected. We therefore conclude that up-regulation of Th2 responses observed after intranasal tolerance induction is an additional or consequential rather than a necessary reaction.
Wolvers
D A
DA
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
van der Cammen
M J
MJ
Kraal
G
G
D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin