REGULATION OF CYTOKINE MESSENGER-RNA EXPRESSION IN ACTIVATED LYMPHOCYTES BY HUMAN CHORIOCARCINOMA JAR CELLS

Because the fetus is semiallogenic to the mother, considerable modulat ion of the maternal immune response must occur in order for pregnancy to be successfully carried to term, Some authors have hypothesized tha t the immunomodulation of pregnancy includes an adjustment of cytokine responses away from the Th1 paradigm and toward the Th2 pattern, In v ivo data from murine pregnancy support this hypothesis. However, in hu mans, the Th1/Th2 model appears to be more complex than that in mice, and cytokine expression of mRNA in human decidual tissue does not refl ect a clear-cut Th2 bias, The experiments described here were undertak en to determine whether and how trophoblastic cells modulate cytokine expression in activated lymphocytes, and whether there is a trend towa rd the use of the Th2 pattern in an experimental model of the maternal -fetal interface, We used reverse transcriptase polymerase chain react ion (rtPCR) to detect cytokine mRNA expression in human peripheral ble ed mononuclear cells cocultivated with human choriocarcinoma JAR cells , We found that although IL-2 (a paradigmatic Th1 cytokine) was signif icantly down-regulated by JAR cells at the mRNA level, similar decreas es were also seen in IL-10, which participates in the Th2 paradigm, We were unable to detect changes in either interferon-gamma (IFN-gamma, a Th1 cytokine) or IL-4 (a Th2 cytokine) mRNA's or in IL-BR expression by fluorescence activated cell sorting, These studies indicate that h uman choriocarcinoma JAR cells are capable of modifying cytokines in a ctivated lymphocytes other than those involved in the Th1 paradigm, Wh ile it may be useful to view human responses against the background of these patterns established hem murine systems, it is reasonable to co nclude that human pregnancy may not involve regulation of Th1 immune r esponses exclusively. (C) 1996 Academic Press, Inc.