title: Gamma delta T lymphocytes regulate the induction and maintenance of oral tolerance.
abstract: Oral administration of Ag, over a period of several days, induces a state of tolerance that is associated with activation of CD8+ T cells that can transfer unresponsiveness to naive syngeneic hosts. We previously demonstrated that these T cells are not CTL precursors and that they inhibit responses by CD8+ CTL, as well as Ab and CD4+ T cell responses. Activation of noncytolytic, CD8+ suppressor T cells by oral Ag is a process that is not understood. In these studies, we asked whether depletion of the gamma delta T cells altered induction of oral tolerance. Injection of the anti-delta-chain Ab (GL3) down-modulated the expression of gamma delta TCR and inhibited the induction of oral tolerance to OVA, as measured by Ab, CD4+, and CD8+ T cell responses. GL3 did not activate IL-2 secretion that could be detected in the serum, nor did it induce IL-2R expression by intraepithelial lymphocytes, suggesting that GL3 inhibited the function of gamma delta T cells rather than activating them. This interpretation is supported by our observation that oral administration of Ag did not induce tolerance in TCR-delta knockout mice. These data suggest that gamma delta T cells play a critical, active role in tolerance induced by orally administered Ag.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ke
authors.forename: K
authors.initials: K
authors.lastname: Pearce
authors.forename: J P
authors.initials: JP
authors.lastname: Lake
authors.forename: H K
authors.initials: HK
authors.lastname: Ziegler
authors.forename: J A
authors.initials: JA
authors.lastname: Kapp
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D016516:CD4-CD8 Ratio; D005434:Flow Cytometry; D051379:Mice; D009055:Mouth / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta