The Hyperresponsiveness of W/Wv Mice to Oral Sensitization Is Associated with a Decrease in TCRγδ-T Cells

We have already reported that WBB6F1-W/Wv (W/Wv) mice, which have mutations in the c-kit gene, are highly susceptible to oral sensitization, and that the proportion of TCRγδ-T cells among the intraepithelial lymphocytes (IELs) (γδ-IELs) of W/Wv is much lower than in congenic wild-type (+/+) mice. In this study we examined an inhibitory role of γδ-IELs in oral sensitization using two different methods. First, wild-type (+/+) mice were sensitized by oral administration of 1.0 mg ovalbumin (OVA) by gavage every day for 9 weeks after anti-TCRγδ antibody treatment 4 times. The treatment resulted in an enhanced OVA-specific IgG1 antibody production, active systemic anaphylaxis (ASA), and Th2-dominant cytokine production. Next, W/Wv mice whose bone marrow cells were reconstituted from C57BL/6J mice for 5 months were sensitized by oral administration of OVA. The OVA-specific IgG1 antibody titer in the bone marrow-reconstituted W/Wv mice was neither significantly enhanced, nor ASA was induced. The proportion of γδ-IELs in the reconstituted mice was much higher than that in the untreated W/Wv mice. The above findings suggest that the decrease or increase in number of γδ-IELs enhances or decreases oral sensitization respectively. These results show that γδ-IELs have an important role in the oral tolerance to food antigens.