title: Spontaneously hypertensive rat: cholera toxin converts suppression to immunity through a Th2 cell-IL-4 pathway.
abstract: The spontaneously hypertensive rat (SHR) exhibits a number of T cell dysfunctions that develop concurrently with elevated blood pressure. Studies have shown a mitogen-induced lymphocyte suppression mediated in part by the production of interferon-gamma (IFN-gamma), which stimulated NO production by macrophages. To assess whether this immune suppression is reversible, SHR were immunized with diphtheria toxoid (DT) with or without cholera toxin (CT) as adjuvant. SHR immunized with DT only displayed weak serum immunoglobulin G (IgG) anti-DT titers, tenfold less than similarly treated normotensive Wistar-Kyoto rats (WKYR). SHR CD4+ T cells failed to proliferate upon in vitro stimulation with DT. In contrast, SHR coimmunized with DT and CT showed serum IgG antibody titers similar to WKYR and Brown Norway rats. Coimmunization with CT rescued SHR CD4+ T cells from suppression and supported DT- or B subunit of CT-specific proliferative responses, and these cells produced more interleukin-4 (IL-4) than IFN-gamma, and anti-IFN-gamma antibody treatment enhanced IL-4 production. Exogenous IL-4 increased the proliferation of antigen-specific CD4+ T cells, whereas IFN-gamma was inhibitory. This study shows that the adjuvant CT induces T helper 2-type responses, reversing the T cell dysfunction in the SHR.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman 59717-3610, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Pascual
authors.forename: M
authors.initials: M
authors.lastname: Coste
authors.forename: P N
authors.initials: PN
authors.lastname: Boyaka
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000818:Animals; D000906:Antibodies / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D004168:Diphtheria Toxoid / Q000494:pharmacology; D007107:Immune System / Q000187:drug effects* / Q000502:physiology; D007109:Immunity / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR / Q000276:immunology* / Q000378:metabolism; D011921:Rats, Inbred WKY; D013601:T-Lymphocytes / Q000473:pathology; D018418:Th2 Cells / Q000502:physiology*
chemical_list: D000906:Antibodies; D004168:Diphtheria Toxoid; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma; D002772:Cholera Toxin