Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes

Biochem Biophys Res Commun. 1998 Apr 28;245(3):933-8. doi: 10.1006/bbrc.1998.8549.


An important prerequisite for a successful pregnancy is that the maternal immune system does not reject the fetus. Down-regulation of the T helper 1 (TH1) associated cellular immune response could therefore be essential. With flow cytometric techniques, we show on a single cell level that both CD4+ and CD8+ T cells from peripheral blood produce less TH1 cytokines (i.e. IFN-gamma and IL-2) and more TH2 cytokines (i.e. IL-4) during normal human pregnancy and shortly after delivery than during non-pregnancy. The TH1/TH2 cytokine ratio in T cells of women during pregnancy and after delivery was significantly decreased. In contrast the TH1/TH2 ratio was elevated to near normal in women with recurrent spontaneous abortions, indicating a marked shift towards TH1 immunity. Fas antigen (CD95) on T cells was significantly elevated during pregnancy and in the post-delivery phase whereas the intracellular expression of anti-apoptotic protein Bcl-2 remained unchanged. Nevertheless Fas-mediated apoptosis in T cells was markedly reduced during normal human pregnancy. We hypothesize that TH1 cells undergo predominantly Fas-mediated apoptosis during pregnancy as has been shown in some TH2-prone diseases (e.g. SLE, HIV) where an elevated Fas expression on peripheral T cells is observed. This could explain the exacerbated occurrence of TH2-associated diseases in pregnancy.

MeSH terms

  • Apoptosis*
  • Down-Regulation*
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lymphocyte Count
  • Pregnancy / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Th1 Cells / physiology*
  • Th2 Cells / physiology*
  • fas Receptor / biosynthesis


  • Interleukin-2
  • Proto-Oncogene Proteins c-bcl-2
  • fas Receptor
  • Interleukin-4
  • Interferon-gamma