Immunologic Research Immunol Res 1996;15:141-150 Marie-Pierre Piccinni Sergio Romagnani Division of Clinical Immunology and Allergy, Institute of Internal Medicineand Immunoallergology, Universityof Florence,Italy *~ ~ 1 7 6 9 J,e~ m* ~ 1 7 6 1 7 6 Key Words Th 1 cells Th2 cells Cytokines Pregnancy Progesterone Relaxin Unexplained recurrent abortion Regulation of Fetal Allograft Survival by Hormone-Controlled Th 1- and Th2-Type Cytokines , * * * * ~ 1 6 9 1 7 6 ~ o * * * * * * , * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * . * * * * * * * o * * . * * * , * Abstract There is clear evidence to suggest that the maternal immune system during pregnancy can enhance or inhibit the develop- ment of the fetoplacental unit. Recent data support the view that some cytokines produced by both T cells and non-T cells (IL-3, GM-CSF, TGF-13, IL-4, IL-10), favor fetal survival and growth. In contrast, other cytokines, such as IFN-7, TNF-13 and TNF-a, can rather compromise pregnancy. Accordingly, we show here that T-ceU clones generated from the decidua of women with unexplained recurrent abortion produced signifi- cantly lower concentrations of IL-4 than clones derived from the decidua of voluntary abortions or the endometrium of nonpregnant women. Thus, despite the complexity of the cyto- kine network, it appears that cytokines favoring the mainte- nance of fetal survival mainly belong to the Th2 pathway, whereas the failure of pregnancy rather associates with the pre- dominance of Th 1-type cytokines and/or the absence of Th2- type cytokines. Interestingly, we also found that, at least in vitro, progesterone promotes the preferential development of Th2-1ike cells and induces transient IL-4 production by estab- lished Thl cells, whereas relaxin, another corpus luteum- derived hormone, mainly promotes the development of Th l- like cells. These data provide an excellent basis for investigat- ing the relationship between the endocrine and the immune system in the regulation of the maternal-fetal interaction. o . . . . e e o e . | Introduction Mammalian reproduction is initiated by the mating of individuals with distinct geno- types and, therefore, mammalian embryos ex- press antigens belonging to both maternal and paternal major histocompatibility complex (MHC). Despite the fact that the embryo, because of the presence of paternal MHC antigens, is alike to an allograft and therefore KARGER E-Mail karger@karger.ch Fax +41 61 306 12 34 http:/Iwww:karger.ch 9 1996 S. KargerAG, Basel 0257-277X/96/0152-0141 $10.00/0 Prof. Sergio Romagnani Istituto di Medicina Intema e lmmunoallergologia Viale Morgagni, 85 1-50134 Firenze (Italy)