Summary
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 α, β or γ (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 (IFNα and γ); (c) increased natural killer cell activity of CBL, 1 week post-infection (p.i.), mediated by IFNγ; (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 IFNγ; (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.
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De Rossi A, Aldovini A, Franchini G, Mann D, Gallo RC, Wong-Staal F (1985) Clonal selection of T lymphocytes infected by cell-free human T-cell leukemia/lymphoma virus type I: parameters of virus integration and expression. Virology 143: 640
De Vecchis L, Graziani G, Macchi B, Grandori C, Pastore S, Popovic M, Gallo RC, Bonmassar E (1985) Decline of natural cytotoxicity of human lymphocytes following infection with human T-cell leukemia/lymphoma virus (HTLV-I). Leukemia Res 9: 349
D'Onofrio C, Perno CF, Mazzetti P, Graziani G, Calio R, Bonmassar E (1988) Depression of early phase of HTLV-I infection in vitro mediated by human interferon β. Br J Cancer 57: 481
D'Onofrio C, Alvino E, Peci E, Calio R, Bonmassar E (1990) Differential interference of α, β or γ interferons with HTLV-I integration and expression. In: Asherson J, Colizzi V, Marini S, Pugliese O (eds) Immunology and biotechnology. Ann Ist Sup Sanità, Roma (in press)
D'Onofrio C, Alvino E, Garaci E, Bonmassar E, Santoro MG (1990) Selection of HTLV-I positive clones is prevented by prostaglandin A in infected cord blood cultures. Br J Cancer 61: 207
Gazzolo L, Duc Dudon M (1987) Direct activation of resting T-lymphocytes by human T-lymphotropic virus type I. Nature 326: 714
Gerli R, Bertotto A, Spinozzi F, Cernetti C, Grignani F, Rambotti P (1986) Phenotypic dissection of cord blood immunoregulatory T-cell subsets by using a two colour immunofluorescence study. Clin Immunol Immunopathol 40: 429
Graziani G, Pasqualetti E, Lopez M, D'Onofrio C, Testi AM, Mandelli F, Bonmassar E (1987) Increased susceptibility of pheripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro. Blood 69: 1175
Herberman RB, Aoki T, Nunn M, Lavrin DH, Sares N, Cradras A, Holden H, Chano HSS (1974) Specificity of51Cr-release cytotoxicity of lymphocytes immune to murine sarcoma virus. J Natl Cancer Inst 53: 103
Macchi B, Popovic M, Allavena P, Ortaldo J, Rossi P, Gallo RC, Bonmassar E (1987) In vitro susceptibility of different human T-cell subpopulations and resistance of large granular lymphocytes to HTLV-I infection. Int J Cancer 40: 1
Macchi B, D'Onofrio C, La Bianca RA, Bonmassar E (1990) Mononuclear cells from peripheral blood of adult donors and from cord blood are equally protected by α and β-interferons against infection with HTLV-I. Pharmacol Res (in press)
Maruyama M, Shibuya H, Harada H, Hatakeyama M, Seiki M, Fujitaa T, Inone J, Yoshida M, Taniguchi T (1987) Evidence for aberrant activation of interleukin 2 autocrine loop by HTLV-I encoded p40x and T3/Ti complex triggering. Cell 48: 343
Matsushima M, Yoneyama A, Nakamura T, Higascihara M, Yatomi Y, Tanabe A, Ohashi T, Oka H, Nakahara K (1987) A first case of complete remission of β-interferon sensitive adult T-cell leukemia. Eur J Haematol 39: 282
Miyajima A, Miyatake S, Schreurs J, De Vries J, Arai N, Yokota T, Arai KI (1988) Coordinate regulation of immune and inflammatory responses by T cell-derived lymphokines. FASEB J 2: 2462
Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Outsuki Y, Shiraishi Y, Nagata K, Hinuma Y (1981) Detection of type C virus particles on a cord blood T-cell line derived by cocultivation of normal human lymphocytes and human leukemic T-cells. Nature 296: 770
Nair MPN, Schwartz SA, Melnonn M (1985) Association of decreased natural and antibody-dependent cellular cytotoxicity and production of natural killer cytotoxic factor and interferon in neonates. Cell Immunol 94: 159
Pesce CD, Ciprani F, D'Onofrio C, Alvino E, Perno CF, Bonmassar E, Caliò R (1987) Low concentrations of suramin can reduce in vitro infection of human cord blood lymphocytes with HTLV-I during long-term culture. Antiviral Res 8: 247
Popovic M, Lange-Wantzin G, Sarin PS, Mann D, Gallo RC (1983) Transformation of human umbilical cord blood T-cells by human T-cell leukemia/lymphoma virus. Proc Natl Acad Sci USA 80: 5402
Popovic M, Sarin PS, Robert-Guroff M, Kalyanaraman VS, Mann D, Minowada Y, Gallo RC (1983) Isolation and transmission of human retrovirus (human T-cell leukemia virus). Science 219: 856
Popovic M, Flomenberg N, Volkman DJ, Mann D, Fauci AS, Dupont B, Gallo RC (1985) Alteration of T-cell functions by infection with HTLV-I or HTLV-II. Science 226: 459
Robert-Guroff M, Ruscetti FW, Posner BJ, Gallo RC (1981) Detection of the human T-cell lymphoma virus p19 in cell of some patients with cutaneous T-cell lymphoma and leukemia using a monoclonal antibody. J Exp Med 154: 1957
Sodroski JC, Rosen CA, Haseltine WA (1984) Trans-acting transcriptional activation of the long-terminal repeat of human T lymphotropic viruses in infected cells. Science 255: 381
Suciu-Foca N, Rubinstein P, Popovic M, Gallo RC, King DW (1984) Reactivity of HTLV-transformed human T-cell lines to MHC class II antigens. Nature 312: 275
Thorn RM, Henney CS (1976) Kinetic analysis of target cell destruction by effector T-cells. I. Delineation of parameters related to the frequency and lytic efficiency of killer cells. J Immunol 117: 2213
Volkmann DJ, Popovic M, Gallo RC, Fauci AS (1985) Human T-cell clones: indiscriminant helper function and lymphokine production. J Immunol 134: 4237
Wong-Staal F, Gallo RC (1985) Human T-lymphotropic retroviruses. Nature 317: 395
Yarchoan R, Guo HG, Reitz MS, Maluish A, Mitsuya H, Broder S (1986) Alterations in cytotoxic and helper T-cell function after infection of T-cell clones with human T-cell leukemia virus type I. J Clin Invest 77: 1466
Yoshida M (1987) Expression of the HTLV-I genome and its association with a unique T-cell malignancy. Biochim Biophys Acta 907: 945
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D'Onofrio, C., Pesce, C.D., Fontana, T. et al. Modulation of the cell-mediated immune function by interferon α, β or γ can partially reverse the immunosuppression induced by human T-cell leukemia virus I in human cord blood cultures. Cancer Immunol Immunother 31, 213–220 (1990). https://doi.org/10.1007/BF01789171
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DOI: https://doi.org/10.1007/BF01789171