Summary
We recently reported that interleukin-2(IL-2)-activated peripheral blood lymphocytes and CD3+, lymphokine-activated killer (LAK) cell clones release tumor necrosis factor α(TNFα) and interferon γ (IFNγ) when stimulated with K562 erythroleukemia cells. We examined the phenotype of IL-2-activated peripheral blood leukocytes that secrete TNFα and IFNγ when stimulated with K562 cells and demonstrated that TNFα secretion is not due to the presence of contaminating mononuclear phagocytes. Further, we demonstrate that IL-2-activated natural killer (NK) cells release only IFNγ when stimulated with K562 cells while T lymphocytes exposed to monoclonal anti-CD3 and K562 cells secrete both TNFα and IFNγ. However, T cells stimulated only with K562 cells did not release IFNγ or TNFα while the admixture of these T cells with NK cells, when stimulated with K562 cells, released levels of TNFα comparable to those produced by the unseparated cells. At present it is unclear whether only one or both effector cell types respond to K562 by releasing TNFα or why the presence both cell types is needed.
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References
Chong AS-F, Aleksijevic A, Scuderi P, Hersh EM, Grimes WJ (1989) Phenotypic and functional analysis of lymphokine activated killer (LAK) cell clones. Ability of CD3+, LAK cell clones to produce interferon-gamma and tumor necrosis factor upon stimulation with tumor targets. Cancer Immunol Immunother 29: 270
Chong AS-F, Scuderi P, Grimes WJ, Hersh EM (1989) Tumor targets stimulate IL-2 activated killer cells to produce interferongamma and tumor necrosis factor. J Immunol 142: 2133
DeVita VT, Hellman S, Rosenberg SA (1989) Cancer principles and practice of oncology, vol 1 2nd edn. Lippincott, Philadelphia, p 301
Djeu JY, Blanchard DK, Richards AL, Friedman H (1988) Tumor necrosis factor induction byCandida albicans from natural killer cells and monocytes. J Immunol 141: 4047
Fiers W, Bronckaert P, Devos R, Fransen L, Haeg G, Leroux-Roels G, Marmenont A, Remant E, Suffys P, Tavernier J, van der Heyden J, von Roy F (1986) Molecular and cellular biology of tumor necrosis factor, interferon gamma and their synergism. In: Cantell K, Schellekens H (eds) The biology of the interferon system. Nijnhoff Dordrecht, p 205
Ghosh AK, Dazzi H, Thatcher N, Moorez M (1989) Lack of correlation between peripheral blood lymphokine-activated killer (LAK) cell function and clinical response in patients with advanced malignant melanoma receiving recombinant interleukin 2. Int J Cancer 43: 410
Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant tumor cells by interleukin-2-activated autologous human peripheral blood lymphocytes. J Exp Med 155: 1823–1841
Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA (1983) Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes. J Exp Med 157: 884
Henkart PA, Yue CC, Yang J, Rosenberg SA (1986) Cytolytic and biochemical properties of cytoplasmic granules of murine lymphokine-activated killer cells. J Immunol 137: 2611
Janicke R, Mannel DN (1990) Distinct tumor cell membrane constituents activate human monocytes for tumor necrosis factor synthesis. J Immunol 144: 1144
Mischell BB, Shilgi SM (1980) Selected methods in cellular immunology. Freeman, New York
Old LJ (1985) Tumor necrosis factor. Science 230: 630
Peters PM, Ortaldo JR, Shalaby MR, Svedersky LP, Nedwin GE, Bringman TS, Hass PE, Aggarwal BB, Herberman RB, Goeddel DV, Palladino MA (1986) Natural killer-sensitive targets stimulate production of TNF-alpha but not TNF-beta (lymphotoxin) by highly purified human peripheral blood large granular lymphocytes. J Immunol 137: 2592
Scuderi P, Sterling KE, Lam KS, Finley PR, Ryan KJ, Ray CG, Petyerson E, Slymen DJ, Salmon SE (1986) Raised serum levels of tumor necrosis factor in parasitic infections. Lancet 2: 1346
Steffen M, Ottomann OG, Moore MAS (1988) Simultaneous production of tumor necrosis factor-alpha and lymphotoxin by normal T cells after induction with IL-2 and anti-T3. J Immunol 140: 2621
Sung S-SJ, Bjorndahl JM, Wang CY, Kao HT, Fu SM (1988) Production of tumor necrosis factor/cachectin by human T cell lines and peripheral blood T lymphocytes stimulated by phorbol myristate acetate and anti-CD3 antibody. J Exp Med 167: 937
Trinchieri G, Perussia B (1988) Immune interferon: a pleiotropic lymphokine with multiple effects. Immunol Today 6: 131
Turner M, Londei M, Feldman M (1988) Human T cells from auto-immune and normal individuals can produce tumor necrosis factor. Eur J Immunol 17: 1807
Wallach D (1986) Cytotoxins (tumor necrosis factor, lymphotoxin and others): Molecular and functional characteristics and interactions with interferons. Interferon 7: 90
Williamson BD, Carswell EA, Rubin BY, Pendergast JS, Old LJ (1983) Human tumor necrosis factor produced by human B-cell lines: synergistic cytotoxic interaction with human interferon. Proc Natl Acad Sci USA 80: 5397
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This work was supported by grants from the national Institutes of Health (CA 23074 and CA 17094) and the Arizona Disease Commission (8277-000000-1-0-YR-9301)
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Chong, A.S.F., Ybarrondo, B., Grimes, W.J. et al. Phenotypic analyses of lymphokine-activated killer cells that release interferon γ and tumor necrosis factor α. Cancer Immunol Immunother 31, 255–259 (1990). https://doi.org/10.1007/BF01789178
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DOI: https://doi.org/10.1007/BF01789178