Original Paper Horm Res 2002;58:128–135 Progesterone Inhibits Rejection of Xenogeneic Transplants in the Sheep Uterus A.C. Majewski P.J. Hansen Department of Animal Sciences, University of Florida, Gainesville, Fla., USA Received: May 2, 2001 Accepted after revision: February 21, 2002 Dr. P.J. Hansen PO Box 110910, University of Florida Gainesville, FL 32611-0920 (USA) Tel. +1 352 392 5590, Fax +1 352 392 5595 E-Mail Hansen@animal.ufl.edu ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2002 S. Karger AG, Basel 0301–0163/02/0583–0128$18.50/0 Accessible online at: www.karger.com/journals/hre Key Words Progesterone W Xenotransplant W Hybridoma cells W Uterine tissue graft Abstract Objectives: One of the proposed roles of progesterone is to prevent maternal immunological destruction of the allogeneic conceptus. Here, it was demonstrated that progesterone allows survival of a xenotransplant placed in the uterine lumen. M ethods: Ovariectomized ewes, surgically prepared to have ligatures around each uter- ine horn, were given daily subcutaneous injections of 50 mg progesterone or vehicle (sesame oil). After 30 days of treatment, mouse hybridoma cells were trans- planted to one ligated uterine horn and phosphate-buff- ered saline was injected into the other horn. The uterus was flushed after an additional 14 days of treatment and hybridoma cells were identified by immunofluores- cence. Results: Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and 1 of 5 vehicle- treated ewes. Immunohistochemical analysis of interca- runcular endometrium using antibodies towards CD8, Á‰, and CD45R lymphocyte markers revealed that local presence of hybridoma cells caused a significant in- crease in CD8+ cells in all tissue compartments. While not significant, the numbers of CD8+ cells in the luminal and glandular epithelium were lower for progesterone- treated ewes. Progesterone tended to increase Á‰ T cell numbers in the glandular epithelium. Conclusions: Re- sults demonstrate that xenograft rejection in the uterus is associated with an increase in CD8+ cells in the endome- trium and that progesterone can inhibit uterine tissue graft rejection responses sufficiently to allow survival or delay rejection of xenograft tissue. Copyright © 2002 S. Karger AG, Basel Introduction The essential hormone for the maintenance of preg- nancy is progesterone [1]. Among its functions, progester- one may be a key hormone for preventing the destruction of the conceptus by the mother’s immune system. Al- though the uterus possesses components of the immune system sufficient to destroy allografts placed within the uterine lumen [2, 3], the pregnant uterus becomes modi- fied to accept antigenically distinct tissue during pregnan- cy. Thus, the conceptus, which is a foreign allograft, rou- tinely survives in the uterus. In some cases, pregnancies as antigenic as those representing xenografts can be success- fully maintained to term [4, 5]. The major evidence that