gamma delta T cells regulate mucosally induced tolerance in a dose-dependent fashion

We used gamma delta TCR-deficient (TCR delta(-/-)) mice to examine the role of gamma delta T cells for induction of mucosal responses and systemic tol erance to high versus low doses of oral antigen. When either TCR delta(-/-) or TCR delta(+/+) mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody respons es were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCR delta(-/-) mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCR delta(-/-) an d TCR delta(+/+) mice given the high dose of OVA, Antigen-induced T(h)1 and T(h)2,cytokine production by splenic CD4(+) T cells was severely inhibited in orally tolerized TCR delta(-/-) and TCR delta(+/+) mice. In contrast, w hile oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCR delta(+/+) mice, the TCR delta(-/-) mi ce were not tolerized and failed to produce IL-10, Our findings indicate th at gamma delta T cells play a significant immunoregulatory role in IL-10-me diated, low-dose oral tolerance induction, but are not essential participan ts in the induction of systemic tolerance to orally introduced antigens giv en in larger doses.