Novel Transforming Growth Factor Betas (TGFβ2) in Pregnancy and Cancer

  • David A. Clark
  • Kathleen C. Flanders
  • Gill Vince
  • Phyllis Starkey
  • Hal Hirte
  • Justin Manuel
  • Jennifer Underwood
  • James Mowbray
Part of the Serono Symposia, USA book series (SERONOSYMP)


A number of cytokines may be present at the fetomaternal interface (1), and these may determine whether the implanted mammalian conceptus will succeed or fail. Certain cytokines have the potential to compromise the pregnancy and cause abortion:tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and interferon γ (IFNγ). This may involve activation of natural killer (NK) lineage cells into lymphokine-activated killer (LAK) cells that have the capacity to damage fetal trophoblast cells (2–7) that lie at the fetomaternal interface and are crucial for placentation and embryo survival (8). Other cytokines have been postulated to be favorable to survival of the pregnancy. Three of these—interleukin-10 (IL-10), granulocyte-macrophage colony stimulating factor (GM-CSF), and transforming growth factor β (TGFβ)—appear to counter those cytokine-dependent processes that are antagonistic to pregnancy. IL-10 does not block generation of LAK cells in response to interleukin-2 (IL-2) (9–13), but can inhibit release of IL-2, TNFα, and related cytokines that are abortogenic. IL-10-deficient mice give birth to babies that are smaller than normal, but apparently do not have a higher resorption (abortion) rate (14). This may be due to the well-known phenomenon of redundancy, whereby several different cytokines produce the same effects, and this preserves a degree of protection when one cytokine is missing. GM-CSF, which is produced by fetal trophoblast (15, 16), has been shown to inhibit the generation of antitrophoblast LAK-like cells in vivo (17 and Clark, Chaouat, Mogil, Wegmann, manuscript submitted). Further, a potent immunosuppressive molecule closely related to TGFβ2 that blocks LAK generation and macrophage activation and cytokine release is also present at the fetomaternal interface (7, 18–20). These TGFβ2-like molecules appear to be released by bone marrow-derived natural suppressor cells and to have unusual molecular properties (20, 21).


Transform Growth Factor Beta Suppressor Cell Suppressive Activity Pregnant Mouse Suppressor Cell Activity 
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Copyright information

© Springer-Verlag New York, Inc. 1994

Authors and Affiliations

  • David A. Clark
  • Kathleen C. Flanders
  • Gill Vince
  • Phyllis Starkey
  • Hal Hirte
  • Justin Manuel
  • Jennifer Underwood
  • James Mowbray

There are no affiliations available

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