Progress 09/15/01 to 09/30/03
Outputs
An experiment was performed to determine whether neonatal treatment of sheep with progestins to ablate uterine glands would eliminate the ability of progesterone to prevent rejection of skin grafts in the uterine lumen. Results indicated that 1) grafts placed in the uterine lumen were rejected in ovariectomized ewes, 2) progesterone prevented rejection, and 3) the effect of progesterone occurred regardless of whether ewes were treated neonatally with progestin. It was found that progestin-treated ewes retained functional uterine glands and it was not possible therefore to evaluate whether progesterone requires active uterine glands for its immunosuppressive activity.
Impacts
Further studies will be required to evaluate the role of progesterone and progesterone-induced secretions from uterine glands on uterine immunology. These studies are underway.
Publications
- Tekin, S., and Hansen, P.J. (2003) Lymphocyte-mediated lysis of sheep chorion: susceptibility of chorionic cells to third-party and maternal cytotoxic lymphocytes and presence of cells in the endometrium exhibiting cytotoxicity toward natural-killer cell targets. Theriogenology 59, 787-800.
- Tekin, S., and Hansen, P.J. (2004) Regulation of numbers of macrophages in the endometrium of the sheep by systemic effects of pregnancy, local presence of the conceptus, and progesterone. Am. J. Reprod. Immunol., in press.
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Progress 10/01/01 to 10/01/02
Outputs
One of the proposed roles of progesterone during pregnancy is to prevent maternal immunological destruction of the allogeneic conceptus. In this experiment, it was demonstrated that progesterone allows the survival of a xenotransplant placed in the uterine lumen. Ovariectomized ewes, surgically prepared to have ligatures placed around each uterine horn, were given daily injections, s.c., of 50 mg progesterone or vehicle (sesame oil). After 30 d of treatment, mouse hybridoma cells were transplanted to one ligated uterine horn and phosphate-buffered saline was injected into the other horn. The uterus was flushed after an additional 14 d of treatment and hybridoma cells were identified by immunofluorescence. Overall, hybridoma cells were recovered from 4/5 progesterone-treated ewes and 1/5 vehicle-treated ewes. Analysis of intercaruncular endometrium using antibodies towards CD8, gamma-delta and CD45R lymphocyte markers revealed that local presence of hybridoma cells
caused a significant increase in CD8+ cells in all tissue compartments. While not significant, the numbers of CD8+ cells in luminal and glandular epithelium were lower for progesterone-treated ewes. Progesterone tended to increase (P=0.07) gamma-delta T cell numbers in glandular epithelium. Results demonstrate that xenograft rejection in the uterus is associated with an increase in CD8+ cells in the endometrium and that progesterone can inhibit uterine tissue graft rejection responses sufficiently to allow survival of xenograft tissue. Natural killer cells (NK) represent an important component of the innate immune system. Although absence of expression of major histocompatibility complex (MHC) proteins on ovine trophoblast makes it potentially a target for NK cells, little is known about regulation of NK cells by products of pregnancy in sheep. Objectives of the present study were to determine whether cells with characteristics of NK cells exist in preparations of ovine peripheral
blood lymphocytes (PBL) and endometrial epithelial cells (EEC) and to determine regulation of such cells by two pregnancy-associated molecules with immunoregulatory properties [ovine uterine serpin (OvUS) and interferon-tau(IFN)]. Ovine PBL and EEC lysed a putative NK target cell, the BHV-1 infected D17 cell, and lysis by both types of cells was neutralized by antibody against a molecule called function-associated molecule (FAM) expressed on NK cells of several species. Moreover, inhibitors that interfere with perforin-mediated lysis blocked NK-like activity of PBL. The NK-like lytic activity of PBL and EEC was inhibited by OvUS while ovine and bovine IFN significantly enhanced NK-like activity of PBL. In conclusion, NK-like activity present in preparations of ovine PBL and EEC is mediated by FAM+ cells, is dependent upon processes that involve perforin processing, and is regulated by OvUS and IFN. Inhibition of NK-like activity of PBL and EEC by OvUS is consistent with a role for
OvUS in protecting the conceptus from maternal cytotoxic lymphocytes. Stimulation of lysis by IFN implies existence of other inhibitory mechanisms during early pregnancy to prevent NK cell-mediated destruction of the conceptus.
Impacts
These data indicate the importance of progesterone and the progesterone-induced secretory protein, ovine uterine serpin, in regulation of uterine immune responses.
Publications
- Tekin, S., and Hansen, P.J. (2002) Natural-killer like cells in the sheep: Functional characterization and regulation by pregnancy-associated proteins. Exp. Biol. Med. 227, 803-811.
- Majewski, A.C., and Hansen, P.J. (2002) Progesterone promotes survival of xenogeneic transplants in the sheep uterus. Hormone Res. 58, 128-135.
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Progress 10/01/00 to 10/01/01
Outputs
no progress - project just initiated
Impacts
(N/A)
Publications
- No publications reported this period
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