MUCOSAL TOLERANCE IS ASSOCIATED WITH, BUT INDEPENDENT OF, UP-REGULATION TH2 RESPONSES

Intranasal administration of protein antigen is an efficient way to in duce mucosal tolerance. Suppressive mechanisms that might be involved in this phenomenon include down-regulation of T-helper type-1 (Th1)-me diated processes by Th2 cells. However, since Th2 responses can also b e subjected to mucosal tolerance, we wanted to investigate whether sup pression of a typical Th1 response, such as a delayed-type hypersensit ivity (DTH) reaction by intranasal tolerance induction, was causally r elated to up-regulation of Th2 responses. We therefore treated mice ei ther systemically or locally with anti-interleukin-4 (IL-4) or anti-IL -10 antibodies before intranasal tolerance induction or before sensiti zation 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 toleranc e as measured by suppression of DTH was not affected. We therefore con clude that up-regulation of Th2 responses observed after intranasal to lerance induction is an additional or consequential rather than a nece ssary reaction.