title: Interferon alpha and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS.
abstract: HIV type 1 (HIV-1) not only directly kills infected CD4(+) T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon alpha (IFNalpha) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNalpha and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNalpha and extracellular Tat. We, therefore, suggest that IFNalpha and Tat may be critical targets for anti-AIDS strategies.
authors.affiliation: Université Pierre et Marie Curie, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Zagury
authors.forename: A
authors.initials: A
authors.lastname: Lachgar
authors.forename: V
authors.initials: V
authors.lastname: Chams
authors.forename: L S
authors.initials: LS
authors.lastname: Fall
authors.forename: J
authors.initials: J
authors.lastname: Bernard
authors.forename: J F
authors.initials: JF
authors.lastname: Zagury
authors.forename: B
authors.initials: B
authors.lastname: Bizzini
authors.forename: A
authors.initials: A
authors.lastname: Gringeri
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
authors.forename: J
authors.initials: J
authors.lastname: Rappaport
authors.forename: M
authors.initials: M
authors.lastname: Feldman
authors.forename: A
authors.initials: A
authors.lastname: Burny
authors.forename: R C
authors.initials: RC
authors.lastname: Gallo
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D015696:Gene Products, tat / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D016898:Interferon-alpha / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D016207:Cytokines; D015696:Gene Products, tat; D016898:Interferon-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus