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Related Experiment Videos

TGF-beta: a possible autocrine immune regulator.

C Lucas1, S Wallick, B M Fendly

  • 1Department of Medicinal, Genetech Inc, South San Francisco, CA 94080.

Ciba Foundation Symposium
|January 1, 1991
PubMed
Summary

Endogenous transforming growth factor-beta 1 (TGF-beta 1) regulates immune cell function. Neutralizing this latent TGF-beta 1 enhances lymphocyte proliferation and impacts immune responses in vivo.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-beta (TGF-beta) is a key immune regulator.
  • Most studies use activated TGF-beta, not endogenously produced latent forms.
  • The autocrine/paracrine role of endogenous latent TGF-beta is understudied.

Purpose of the Study:

  • To investigate the role of endogenously produced latent TGF-beta 1 in immune regulation.
  • To assess the impact of neutralizing latent TGF-beta 1 during lymphocyte activation.
  • To explore the function of latent TGF-beta 1 produced by tumor cells.

Main Methods:

  • Used monoclonal antibody (mAb) 4A11 to detect and neutralize endogenous TGF-beta 1.
  • Stimulated peripheral blood mononuclear cells (PBMC) with interleukin 2 or PHA/TPA.
  • Utilized engineered CHO cell lines producing latent TGF-beta 1 in vivo and in vitro models.

Main Results:

  • PBMC secrete significant latent TGF-beta 1 upon stimulation.
  • Neutralizing TGF-beta 1 with mAbs enhances PBMC proliferation.
  • Latent TGF-beta 1-producing CHO cells suppressed cytotoxic T lymphocyte generation and natural killer cell activity.

Conclusions:

  • Mechanisms exist to activate latent TGF-beta in vitro and in vivo.
  • Latent TGF-beta 1 acts as an autocrine/paracrine regulator of immune functions.
  • Tumor cell-derived latent TGF-beta 1 may play a role in immune surveillance evasion.

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