Progesterone Inhibits Rejection of Xenogeneic Transplants in the Sheep Uterus

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. Methods: Ovariectomized ewes, surgically prepared to have ligatures around each uterine horn, were given daily subcutaneous injections of 50 mg progesterone or vehicle (sesame oil). After 30 days 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 days of treatment and hybridoma cells were identified by immunofluorescence. Results: Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and 1 of 5 vehicle-treated ewes. Immunohistochemical analysis of intercaruncular endometrium using antibodies towards CD8, γδ, 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 the luminal and glandular epithelium were lower for progesterone-treated ewes. Progesterone tended to increase γδ T cell numbers in the glandular epithelium. Conclusions: 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 or delay rejection of xenograft tissue.

Interactions between negative energy balance, metabolic diseases, uterine health and immune response in transition dairy cows

“…Among the regulatory processes responsible for inhibition is an immunosuppressive role for progesterone (Majewski and Hansen, 2002;Padua et al, 2005) as well as differentiation of regulatory immune cells that can inhibit inflammation and T cell responses. Among these cells are the M2 macrophage (Gustafsson et al, 2008;Oliveira et al, 2010), γδ T cell (Lee et al, 1992;Suzuki et al, 1995), a n d T r e g c e l l ( A l u v i h a r e e t a l .…”

Secretary IgA Concentrations and plasma Cell Count Changes Associated with the Estrous Cycle in Ewes

“…During luteal phase or pregnancy, the secretions of the cervical glands become more viscous, forming a plug of thickened mucous in the orifice of the cervix, thus, preventing the coming in of sperm and microorganisms into the uterus [13] . In sheep, one of the progesterone actions is to reduce numbers of specific populations of lymphocytes in the layers of uterine endometrium and hybridoma xenografts [17] . It also played role by hinders rejection or enhances survival of skin allografts placed within the uterine lumen [9] .…”

Immunoendocrine aspects of endometrial function and implantation

“…Nevertheless, in the ovine uterus, low concentrations of progesterone can block tissue graft rejection (Majewski & Hansen 2002, and this has been associated with the induction of a uterine immunoregulatory protein belonging to the serpin family of proteinase inhibitors (see later). The accumulation of macrophages and gd T-cells in the ovine uterus during pregnancy also appears to be partly under sex steroid regulation (Tekin & Hansen 2004).…”

“…Studies in sheep and hamsters illustrate that progesterone at concentrations found at the maternal-foetal interface can inhibit tissue graft rejection in utero (Moriyama & Sugawa 1972, Majewski & Hansen 2002. In terms of local effects of progesterone on endometrial/decidual uNK cells, the majority of studies suggest that the immunomodulatory activity may be indirect.…”