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Augmentative effect ofNocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s)

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Summary

Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3− CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNFα, anti-IL-1α, or anti-IL-1β antibodies. Furthermore, no tumor necrosis factor-α (TNFα), TNFβ, IL-1α, β, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNFα, TNFβ, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.

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Authors and Affiliations

  1. 3rd Department of Internal Medicine, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, 553, Osaka, Japan

    Takuma Shirasaka, Ichiro Kawase, Masaji Okada, Misa Kitahara, Toshiyuki Ikeda, Kiyoshi Komuta, Shigeto Hosoe, Soichiro Yokota, Tomiya Masuno & Susumu Kishimoto

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  1. Takuma Shirasaka
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  2. Ichiro Kawase
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  3. Masaji Okada
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  4. Misa Kitahara
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  5. Toshiyuki Ikeda
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  6. Kiyoshi Komuta
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  7. Shigeto Hosoe
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  8. Soichiro Yokota
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  9. Tomiya Masuno
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  10. Susumu Kishimoto
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This work was supported by a Grant-in-aid for Cancer Research from the Ministry of Education, Science, and Culture of Japan

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Shirasaka, T., Kawase, I., Okada, M. et al. Augmentative effect ofNocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s). Cancer Immunol Immunother 30, 195–204 (1989). https://doi.org/10.1007/BF01665005

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  • DOI: https://doi.org/10.1007/BF01665005

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