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Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
Abstract
Type beta transforming growth factor (TGF-beta) is a unique polypeptide that has been isolated from a number of different tissues and can induce the phenotypic transformation of non-neoplastic fibroblasts as measured by the stimulation of their growth in soft agar. Recently, TGF-beta has been demonstrated to exert profound inhibitory effects on T and B lymphocyte proliferation. In this study, the effects of TGF-beta on natural killer (NK) cell function were investigated. After 20 hr of culture in the presence of TGF-beta, the NK activity of peripheral blood lymphocytes (PBL) was significantly reduced compared with PBL cultured in medium alone. Similarly, TGF-beta produced a significant depression in the cytolytic activity of highly enriched large granular lymphocytes (LGL). This effect of TGF-beta appeared to be mediated directly on the effector cells, because cultivation of the K562 target cells in TGF-beta did not affect target cell susceptibility to lysis. Binding studies with 125I-TGF-beta indicated that LGL possess approximately 1400 high-affinity (Kd = 1PM) receptors/cell, which represents a considerably higher affinity receptor for TGF-beta than that found on fibroblasts. Culturing of PBL and LGL in TGF-beta resulted in a marked blunting of the boosting of NK cytolysis by interferon-alpha but not by interleukin 2, which suggested that TGF-beta may down-regulate interferon-alpha receptors on NK cells. These results, indicate that in addition to inhibitory effects on T and B cells, TGF-beta also inhibits NK cell function. Although the in vivo role of TGF-beta is presently undefined, it may be an important immunoregulatory protein that has a negative influence on lymphocyte activation.
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Cited by
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985
Biology of Natural Killer Cells
Trinchieri, G. (1989) · Advances in Immunology · doi:10.1016/s0065-2776(08)60664-1 · Cited by 2,902
NATURAL KILLER CELLS IN ANTIVIRAL DEFENSE: Function and Regulation by Innate Cytokines
Biron, C. A., Nguyen, K. B., Pien, G. C., Cousens, L. P., & Salazar-Mather, T. P. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.189 · Cited by 2,113
Non-small cell lung cancer: current treatment and future advances
Zappa, C., & Mousa, S. A. (2016) · Translational Lung Cancer Research · doi:10.21037/tlcr.2016.06.07 · Cited by 1,944
The polarization of immune cells in the tumour environment by TGFβ
Flavell, R. A., Sanjabi, S., Wrzesinski, S. H., & Licona-Limón, P. (2010) · Nature Reviews Immunology · doi:10.1038/nri2808 · Cited by 940
Metadata
- Authors
- Rook, A. H., Kehrl, J. H., Wakefield, L. M., Roberts, A. B., Sporn, M. B., Burlington, D. B., Lane, H. C., & Fauci, A. S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1986-05
- Volume
- 136
- Issue
- 10
- Pages
- 3916-3920
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1539607590
- Cited by
- 570
- References
- 0
- FWCI
- 10.31
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. https://app.cochat.ai/papers/10.4049/jimmunol.136.10.3916
- The paper
- Rook, A. H., Kehrl, J. H., Wakefield, L. M., Roberts, A. B., Sporn, M. B., Burlington, D. B., Lane, H. C., & Fauci, A. S. (1986). Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. The Journal of Immunology. https://doi.org/10.4049/jimmunol.136.10.3916
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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