Priming of systemic and local delayed-type hypersensitivity responses by feeding low doses of ovalbumin to mice (1)
When oral tolerance of systemic DTH responses can be prevented in mice fed OVA, an active DTH response can be induced in the intestinal mucosa after oral challenge with OVA. One factor which has hindered direct proof of this hypothesis is that in our earlier studies, a mucosal DTH response could only be revealed by treating mice with potent immunomodulators before feeding OVA.
All mice fed 5 mg OVA or more had significantly suppressed systemic DTH responses and antibody responses. When the dose of fed antigen was further reduced to 10 ug, significant enhancement of the systemic DTH. Mice fed 10 ug OVA had significantly enhanced DTH responses compared with controls and this effect was somewhat more marked in mice fed 50 ug OVA. Neither dose of fed OVA had any effect on serum IgG antibody responses.
After oral challenge with OVA, mice primed with 1, 5 or 20 mg OVA had villus and crypt lengths and CCPR which were not significantly different from those in saline-fed controls challenged with OVA. In addition, these mice had IEL counts which were identical to control values. mice fed 10 ug OVA had a significant increase in IEL count on challenge with OVA compared with controls. After oral challenge with OVA, mice primed orally with 50 ug OVA had significant increases in crypt length and in CCPR.
Two groups of animals received either 50 ug OVA or 0.2 ml saline orally, and some of these mice were tested for systemic DTH responses by footpad challenge 1-6 days later. Mice fed OVA had a significantly larger footpad response than controls on Day 4. However, this DTH response was very small and was never found at other times after feeding OVA.
Entirely consistent with studies in rats found that IgE antibody responses could be elicited by feeding 10 ug OVA, whereas higher doses (> 100 ug) produced systemic tolerance. The ability of fed proteins to prime for systemic DTH is a highly unusual phenomenon induced by a very narrow range of antigen dose. That oral tolerance to dietary proteins can be overcome in normal animals, as well as by the immunomodulatory regimes used previously, has important implications for clinical food-sensitive enteropathy.