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Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells

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Summary

The effect(s) of purified transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) on the induction and function of lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) was examined. The addition of TGF-beta, but not PDGF, to cultures containing fresh C57BL/6 mouse splenocytes or human peripheral blood lymphocytes plus recombinant interleukin-2 markedly inhibited the development of mouse and human LAK cell activity (measured after 3 days for cytotoxicity against cultured or fresh tumor targets in 4-h 51Cr release assays). The addition of TGF-beta, but not PDGF, to a one-way, C57BL/6 anti-DBA/2, mixed lymphocyte reaction effectively blocked the generation of allospecific CTL as well. However, TGF-beta did not inhibit the effector function of LAK cells or of allospecific CTL when added directly to the short-term cytolytic assay. A second form of homodimeric TGF-beta, type 2, was also found to be suppressive on the development of murine LAK cells and allospecific CTL. Collectively, these data demonstrate that the peptide TGF-beta is a potent inhibitor of LAK cell and CTL generation in vitro.

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Authors and Affiliations

  1. Surgery Branch, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    James J. Mulé, Susan L. Schwarz & Steven A. Rosenberg

  2. Laboratory of Chemoprevention, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, USA

    Anita B. Roberts & Michael B. Sporn

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  1. James J. Mulé
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  2. Susan L. Schwarz
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  3. Anita B. Roberts
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  4. Michael B. Sporn
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  5. Steven A. Rosenberg
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Mulé, J.J., Schwarz, S.L., Roberts, A.B. et al. Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother 26, 95–100 (1988). https://doi.org/10.1007/BF00205600

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  • DOI: https://doi.org/10.1007/BF00205600

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