title: Modulation of the cell-mediated immune function by interferon alpha, beta or gamma can partially reverse the immunosuppression induced by human T-cell leukemia virus I in human cord blood cultures.
abstract: Infection with human T-cell leukemia virus type I (HTLV-I) is associated in vitro and in vivo with a remarkable depression of cell-mediated immune functions. In the present report it is shown that early events following virus-induced suppression of the cell-mediated immune response of freshly isolated cord blood mononuclear cells (CBL) infected with HTLV-I can be partially counteracted by treatment with interferons alpha, beta or gamma (IFN). All three types of IFN exerted a protective effect on CBL cultures exposed to the virus. This resulted in: (a) a reduced number of virus-positive cells until 4 weeks of culture; (b) delay in the clonal expansion of infected cells (IFN alpha and gamma); (c) increased natural killer cell activity of CBL, 1 week post-infection (p.i.), mediated by IFN gamma; (d) increase of allospecific recognition of infecting and priming HTLV-I donor MT-2 cells by CBL in a cytotoxic-T-lymphocyte-like response, mediated by IFN and particularly by IFN gamma; (e) phenotype distribution of CBL subpopulations, tested 4 days p.i., more similar to that of non-infected CBL cultures. In contrast, the overall CBL proliferation, that is profoundly depressed during the first week p.i., was not restored by IFN treatments, suggesting that boosting of the cell-mediated killing induced by IFN might involve the maturation of undifferentiated precursor cells rather than stimulation of their proliferation. The improvement of the efficiency of the antiviral immune response induced by treatment with IFN is likely to contribute to the clearance of virus-positive cells during the early phase of infection. This would provide experimental evidence to support an immunopharmacological approach contributing to the conversion of HTLV-I carriers from positive to negative.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, II University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: D'Onofrio
authors.forename: C D
authors.initials: CD
authors.lastname: Pesce
authors.forename: T
authors.initials: T
authors.lastname: Fontana
authors.forename: F
authors.initials: F
authors.lastname: Ciprani
authors.forename: E
authors.initials: E
authors.lastname: Bonmassar
authors.forename: R
authors.initials: R
authors.lastname: Caliŏ
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000276:immunology; D005312:Fetal Blood / Q000382:microbiology*; D015490:HTLV-I Infections / Q000188:drug therapy / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008214:Lymphocytes / Q000502:physiology; D010641:Phenotype; D014407:Tumor Cells, Cultured
chemical_list: D007370:Interferon Type I; D007371:Interferon-gamma