1-2-dioleoyloxy-3-(trimethylammonium)propane and aluminum-sulfate

In the following study, we demonstrate that medium responder PVG rats immunized i.p. with OVA complexed to the adjuvant aluminum hydroxide exhibit a moderate IgE response (400-1000 ng/ml). In these rats, we demonstrate that underlying the MHC class II-restricted CD4+ T cell response, there is an MHC class I-restricted CD8+ T cell component that plays an important role in restricting the magnitude and duration of the IgE response. We show that in vivo depletion of CD8+ T cells effects a massive increase in IgE (20-fold), and that they are MHC class I-restricted, OVA-specific, cytolytic cells that universally produce IFN-gamma (25-69 ng/ml) and IL-2 (7.6-22 U/ml), and occasionally secrete IL-4 (68-81 U/ml IL-4), and when adoptively transferred into CD8-depleted recipients, can effect a significant reduction in IgE (3- to 50-fold). We also demonstrate that this in vivo inhibition of IgE is dependent on the Ag-specific activation of the CD8+ T cells, and that the activated CD8+ T cells will suppress total/bystander IgE in an Ag-nonspecific manner. These data are consistent with a growing literature demonstrating sensitization of MHC class I-restricted CD8+ T cells by exogenous protein Ags delivered to mucosal sites, and may represent a mechanism whereby a selective pressure can be applied on the functional outcome of an immunoglobulin response to environmental allergens.

Topics: Adoptive Transfer; Alum Compounds; Animals; Antibodies, Blocking; Antibodies, Monoclonal; Antigen-Presenting Cells; CD3 Complex; CD4 Antigens; CD8 Antigens; Cells, Cultured; Clone Cells; Cytotoxicity, Immunologic; Drug Combinations; Epitopes; Fatty Acids, Monounsaturated; Female; Fluorescent Dyes; Hemocyanins; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Immunoglobulin E; Interferon-gamma; Interleukin-2; Interleukin-4; Lymph Nodes; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Depletion; Mollusca; Ovalbumin; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Receptors, Antigen, T-Cell, alpha-beta; Receptors, Antigen, T-Cell, gamma-delta; Stem Cells; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Trypsin