Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0405186 on July 20, 2005

Published online before print July 20, 2005
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(Journal of Leukocyte Biology. 2005;78:946-953.)
© 2005 by Society for Leukocyte Biology

Species differences in the effect of pregnancy on lymphocyte cytokine production between human and rat

Marijke M. Faas*,1, Annechien Bouman{dagger}, Angelique L. Veenstra van Nieuwenhoven{dagger}, Gerda van der Schaaf*, Henk Moes*, Maas Jan Heineman{dagger} and Paul de Vos*

* Transplantation Biology and Immunoendocrinology, Division of Medical Biology, Department of Pathology and Laboratory Medicine, and
{dagger} Department of Obstetrics and Gynecology, University Medical Centre Groningen and University of Groningen, The Netherlands

1Correspondence: Transplantation Biology and Immunoendocrinology, Division of Medical Biology, Department of Pathology and Laboratory Medicine, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. E-mail: m.m.faas{at}med.umcg.nl

In the present study, we evaluated whether lymphocyte cytokine production during human and rat pregnancy shifts toward T helper cell type 2 (Th2) cytokine production. Therefore, blood samples were taken during the follicular and luteal phase and during pregnancy in rats and humans. Whole blood was ex vivo-stimulated with phorbol 12-myristate 13-acetate and calcium ionophore and intracellular interferon-{gamma} (IFN-{gamma}) and interleukin (IL)-4 production, and the percentage of cells in the various lymphocyte populations was measured using flow cytometry. Rats and humans adapted their immune responses to pregnancy but have different strategies: During human pregnancy, the percentage of lymphocytes producing IFN-{gamma} was decreased, and the percentage IL-4-producing lymphocytes was not affected. The rat adapts its immune response to pregnancy by decreasing the total number of the various lymphocyte populations, and the percentage of IFN-{gamma}- or IL-4-producing lymphocytes was not affected or increased (% IFN-{gamma}-producing cytotoxic lymphocytes). It is speculated that during rat pregnancy, there is no need to decrease the number of IFN-{gamma}-producing lymphocytes, as in nonpregnant rats, the total number of IFN-{gamma}-producing lymphocytes after stimulation is relatively low, and there is no necessity for a further decrease. In nonpregnant humans, the percentage IFN-{gamma}-producing lymphocytes is much higher and probably dangerous for pregnancy, and therefore, this percentage needs to decrease during pregnancy. In conclusion, although the data from humans concur with the Th1/Th2 paradigm, the data from rats do not concur with this paradigm. The present studies therefore challenge the classical Th1/Th2 paradigm during pregnancy.

Key Words: interferon-{gamma} • interleukin-4 • NK cells • luteal phase • follicular phase






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