title: Modulation of Th1/Th2 immune responses to HIV-1 Tat by new pro-GSH molecules.
abstract: We have previously demonstrated that in Ova-immunized mice the increase in intra-macrophage thiol pool induced by pro-GSH molecules modulates the Th1/Th2 balance in favour of a Th1-type immune response. We show now that the same molecules can support a Th1-type over Th2-type immunity against Tat, which is an early HIV-1 regulatory protein and a Th1 polarizing immunomodulator that is increasingly considered in new anti-HIV vaccination strategies. Our results indicate that Tat-immunized mice pre-treated with the C4 (n-butanoyl) derivative of reduced glutathione (GSH-C4) or a pro-drug of N-acetylcysteine (NAC) and beta-mercaptoethylamine (MEA) (I-152), have decreased levels of anti-Tat IgG1 as well as increased levels of anti-Tat IgG2a and IgG2b isotypes suggesting a Th1-type response. Moreover, Th1-(IFN-γ and IL-2) Ag-specific cellular responses were detected by ELISPOT assay in splenocytes of the same animals as well as an increase of IL-12 levels in the plasma. These findings suggest that the Th1 immune response to HIV-1 Tat could be further polarized by these molecules. These results together with those previously reported suggest that pro-GSH molecules could be used to modulate the immune response towards different antigens and may be further exploited for inducing specific Th1 immune responses against other HIV antigens as well as other intracellular pathogens in new Tat-based vaccination protocols.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi, 2, 61029 Urbino (PU), Italy. alessandra.fraternale@uniurb.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fraternale
authors.forename: Maria Filomena
authors.initials: MF
authors.lastname: Paoletti
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dominici
authors.forename: Costantina
authors.initials: C
authors.lastname: Buondelmonte
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Arianna
authors.initials: A
authors.lastname: Castaldello
authors.forename: Antonella
authors.initials: A
authors.lastname: Tripiciano
authors.forename: Aurelio
authors.initials: A
authors.lastname: Cafaro
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palamara
authors.forename: Rossella
authors.initials: R
authors.lastname: Sgarbanti
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000494:pharmacology; D000111:Acetylcysteine / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D003543:Cysteamine / Q000276:immunology / Q000494:pharmacology; D018604:Epitope Mapping / Q000379:methods; D005260:Female; D005978:Glutathione / Q000276:immunology* / Q000494:pharmacology; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007155:Immunologic Factors; D007376:Interleukin-2; D011355:Prodrugs; D054322:tat Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D003543:Cysteamine; D007371:Interferon-gamma; D005978:Glutathione; D000111:Acetylcysteine