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

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‐γ (IFN‐γ) 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‐γ 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‐γ‐ or IL‐4‐producing lymphocytes was not affected or increased (% IFN‐γ‐producing cytotoxic lymphocytes). It is speculated that during rat pregnancy, there is no need to decrease the number of IFN‐γ‐producing lymphocytes, as in nonpregnant rats, the total number of IFN‐γ‐producing lymphocytes after stimulation is relatively low, and there is no necessity for a further decrease. In nonpregnant humans, the percentage IFN‐γ‐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.