Diminished natural killer activity in pregnancy: modulation by interleukin 2 and interferon gamma.
We investigated the alterations of natural killer (NK) cells in pregnancy, which led to decreased killing from the first trimester to the puerperium. We show that this phenomenon cannot be ascribed to a defective number of NK cells since the amounts of HNK-1+, CD16+ (Leu 11), and CD11b+ (OKM1) cells were within normal ranges. Recombinant interleukin 2 (rIL-2) corrects the functional defect in a dose and time-dependent manner, without modification in the surface phenotype of the population. Analysis of the pattern of target cell susceptibility to lysis, together with the similar ability of recombinant interferon gamma (rIFN-gamma) to correct the deficiency, and CD16+, CD3- phenotype of the precursor and effector lymphocytes, demonstrated that the induced cytotoxicity was mediated by NK cells. Inhibitors in pregnancy sera block IL-2 production by specific T cells, but we show that they do not influence either NK activity or its reconstitution by rIL-2. These findings place the deficiency at the level of NK cell maturation into cytotoxic effector lymphocytes. Thus, homeostasis of the NK activity of pregnant women may provide a biological model for clarifying the internal mechanisms regulating NK-cell activation in vivo. Present studies in vitro suggest that modulation of lymphokine production may play a role in the adaptive response of NK cells in pregnancy.
D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007958:Leukocyte Count; D049590:Postpartum Period / Q000276:immunology; D011247:Pregnancy / Q000097:blood / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma