The goals of this application are to explore the role of interleukin-2 (IL-2) and IL-2 receptor in the human placenta. The investigators have identified the placenta as a source of this cytokine, and have shown that the placenta of Type I diabetic women fail to elaborate the mRNA for IL-2. Preliminary evidence suggests that the placental form of the molecule is different from that produced by the T-cell, and the investigators propose to sequence the cDNA for placental IL-2 in order to elucidate potential functional and regulatory differences. In addition, the expression of IL-2 receptors will be studied by Northern analysis and in situ hybridization in both normal and diabetic placentas, in order to explore the possibility that receptor production is also affected in Type I diabetic placenta. Other potential regulators of placental IL-2 will also be examined for their ability to modulate levels of either the cytokine or its receptor. These include mitogens, which induce T- lymphocyte production of IL-2, as well as glucose which the investigators suggest as a potential regulator of an IL-2/IL-2 receptor autocrine loop in this tissue. Finally, transgenic mice will be generated which either over- or underexpress placental IL-2, in order to examine the role of this cytokine in an in vivo setting, to elucidate the function of this molecule in placental and fetal development.
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