Shifts in the TH1/TH2 balance during human pregnancy correlate with apoptotic changes.
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.
Reinhard
G
G
Department of Clinical Biochemistry, University of Bonn, Germany. lab04@mailer.meb.uni-bonn.de
Noll
A
A
Schlebusch
H
H
Mallmann
P
P
Ruecker
A V
AV
D017209:Apoptosis; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018655:Lymphocyte Count; D011247:Pregnancy / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D019014:fas Receptor / Q000096:biosynthesis
D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D015847:Interleukin-4; D007371:Interferon-gamma