ABSTRACT
The biologic role and repertoire of cells bearing the gamma delta T cell receptor has not been fully defined. However, their tropism for epithelial microenvironments is recognized and suggests an important role for these cells in immune defense at mucosal tissue surfaces. The study presented below utilizes an experimental model in which repeated exposure of Brown Norway rats to OVA by inhalation induces a state of Ag-specific, IgE isotype-specific "tolerance" via immune deviation. This process seems similar to oral tolerance in the gut. This form of tolerance was adoptively transferred to naive syngeneic recipients by i.p. injection of as few as 10(3) positively selected TCR-gamma delta+ cells from OVA-exposed rats. These TCR-gamma delta+ T-cells are demonstrated to produce high levels of INF-gamma in response to OVA stimulation, and this provides a potential mechanism for the inhibition of Th2 cell proliferation, resulting in suppression of IgE production. The unique potency of these cells in selective suppression of IgE Ab production in response to natural "mucosal" Ag exposure suggests a potentially important role in protection against primary allergic sensitization in vivo.
Subject(s)
Immunoglobulin E/biosynthesis , Receptors, Antigen, T-Cell, gamma-delta/immunology , T-Lymphocyte Subsets/immunology , Administration, Inhalation , Allergens/immunology , Animals , Antigens, Dermatophagoides , Cell Line , Down-Regulation/immunology , Glycoproteins/administration & dosage , Glycoproteins/immunology , Immunoglobulin E/immunology , Immunoglobulin G/biosynthesis , Male , Ovalbumin/administration & dosage , Ovalbumin/immunology , Rats , Rats, Inbred BN , Rats, Sprague-DawleyABSTRACT
Indirect evidence implicates gamma delta T cells in the cross-regulation of CD4 alpha beta T cell responses. Adoptive transfer of small numbers of gamma delta T cells from ovalbumin (OVA)-tolerant mice selectively suppressed TH2-dependent immunoglobulin E (IgE) antibody production without affecting parallel IgG responses. Challenge of these gamma delta T cells in vitro with specific antigen resulted in production of high levels of interferon gamma. The effects of the gamma delta T cells may be mediated by direct inhibition of OVA-specific CD4+ TH2 cell proliferation or selection for specific CD4 TH2 cells.