Ovalbumin-specific, MHC class I-restricted, alpha beta-positive, Tc1 and Tc0 CD8+ T cell clones mediate the in vivo inhibition of rat IgE.
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.
MacAry
P A
PA
Department of Immunology, King's College School of Medicine and Dentistry, London, United Kingdom.
Holmes
B J
BJ
Kemeny
D M
DM
D019264:Adoptive Transfer; D000534:Alum Compounds; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004338:Drug Combinations; D000939:Epitopes / Q000276:immunology*; D005229:Fatty Acids, Monounsaturated; D005260:Female; D005456:Fluorescent Dyes; D006433:Hemocyanins / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008974:Mollusca; D010047:Ovalbumin / Q000276:immunology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis; D013234:Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014357:Trypsin
D000534:Alum Compounds; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D004338:Drug Combinations; D000939:Epitopes; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D000644:Quaternary Ammonium Compounds; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; C041524:aluminum sulfate; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D006433:Hemocyanins; D014357:Trypsin; C032808:keyhole-limpet hemocyanin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane