Evidence that TGF-beta can inhibit human T-lymphocyte proliferation through paracrine and autocrine mechanisms

Cell Immunol. 1993 Aug;150(1):45-58. doi: 10.1006/cimm.1993.1177.


Transforming growth factor-beta (TGF-beta) has been documented as having an inhibitory effect on the proliferation and growth of human T-lymphocytes. We examined the relative contribution of both exogenous and endogenous TGF-beta to this inhibitory action. Purified human peripheral blood T-cells were cultured with Con A (0.2 microgram/ml), washed with methyl mannopyranoside, and then cultured in rIL-2 (5 U/ml) with or without TGF-beta (80 pM). Proliferation, as measured by uptake of tritiated thymidine at 72 hr, was inhibited by added active TGF-beta. Addition of neutralizing anti-TGF-beta antibodies at the initiation of culture abrogated the antiproliferative effects of TGF-beta. A mink lung cell bioassay was used to measure endogenous TGF-beta production by the T-cells following transient acidification of the supernatants to activate latent TGF-beta. T-lymphocytes cultured with rIL-2 alone produced low levels of TGF-beta, first detectable at 72 hr. The addition of (active) TGF-beta to these cultures resulted in earlier and higher levels of endogenously produced latent TGF-beta protein. This was reflected at the mRNA level as well. The exogenously added active TGF-beta appeared to be depleted during the culture period, presumably by the activated T-cells, which exhibited elevated levels of types I, II, and III TGF-beta receptors. The increase in TGF-beta protein levels was due to endogenous TGF-beta synthesis and secretion as supported by a capture assay using 35S-labeled culture supernatants. These findings indicate that both paracrine and autocrine mechanisms are involved in the inhibitory effects of TGF-beta on the proliferation of normal human T-lymphocytes and suggest that other TGF-beta-producing cells can augment production of TGF-beta by activated T-lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Drug Administration Schedule
  • Gene Expression / drug effects
  • Humans
  • Interleukin-2 / administration & dosage
  • Lymphocyte Activation / drug effects*
  • RNA, Messenger / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Transforming Growth Factor beta
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology*


  • Interleukin-2
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta