Deviations in populations of peripheral blood mononuclear cells and endometrial macrophages in the cow during pregnancy

Abstract

The presence of conceptus alloantigens necessitates changes in maternal immune function. Here, we used the cow to evaluate whether species with epitheliochorial placentation have changes in specific leukocyte populations during pregnancy similar to those reported in species with hemotropic placentae. At days 33-34 of pregnancy, there was no effect of pregnancy status on the number of cells positive for CD8, CD4, gdT cell receptor, or the monocyte marker CD68 in the peripheral blood mononuclear cell (PBMC) population. There was, however, an increase in the proportion of CD4 C cells that were positive for CD25. There was no effect of status on the proportion of PBMCs that were CD8C when comparing preparturient cows to nonpregnant cows. However, preparturient cows had an increased percentage of PBMCs that were gdT cells and CD4 C CD25C and a tendency for a lower percentage that were CD68 C cells. Using immunolocalization with anti-CD68, it was found that pregnant cows had increased numbers of CD68 C cells in the endometrial stroma as early as days 54-100 of gestation; this increase persisted through the last time examined (day 240 of gestation). Cells positive for CD68 were also positive for another macrophage/monocyte marker, CD14. In conclusion, pregnancy in the cow is associated with changes in peripheral and endometrial leukocyte numbers, which are similar to patterns observed in other species.

Gene Expressions in the Persistent Corpus Luteum of Postpartum Dairy Cows: Distinct Profiles from the Corpora Lutea of the Estrous Cycle and Pregnancy

“…In turn, the persistent CL might survive for a long period without changes in the tolerance of the local immune system. In fact, Oliveira et al [35] reported that Treg concentrations were elevated in the peripheral blood lymphocytes of pregnant cows between days 33 and 34 of gestation, the same period of pregnancy examined in the present study. TGFβ is a multifunctional cytokine and regulates T-cell growth and development; TGFβ converts naive T cells to Tregs with upregulation of IL-2, while TGFβ and inflammatory cytokine IL-6 induce differentiation of Th 17 to stimulate inflammation [39].…”

PGF2α levels in Day 8 blood plasma are increased by the presence of one or more embryos in the uterus

“…Using a multiple embryo transfer (ET) model, we found several differentially expressed proteins (DEP) in the uterine fluid (UF) on day 8 (Muñoz et al, 2012;Gómez et al, 2013); some of these UF proteins are submitted to different bilateral regulations between horns (Trigal et al, 2014). The UF interface is representative of interactions between embryos, endometrium and immune cells in utero, which can also affect conceptus and endometrial growth by increasing the concentration of cytokines (Leung et al, 2000;Oliveira and Hansen, 2008;Ideta et al, 2010;Muñoz et al, 2012). The UF contains not only live cells (immune, detached endometrial) but also secreted products and cell debris, such as epithelial cells that are in constant renewal and extrusion into the lumen (Welsh 1993;Fahey et al, 2006).…”

The role of placental MHC class I expression in immune-assisted separation of the fetal membranes in cattle

“…In spite of this, the high risk of RFM in MHC class I compatible pregnancies (Benedictus et al, 2012;Joosten et al, 1991) and the direct effect of MHC class I compatibility on the maternal immune response in the uterus (Davies et al, 2004) shows that an adaptive immune response to fetal MHC class I is also critical for separation of the fetal membranes. Compared to macrophage numbers (Miyoshi et al, 2002;Oliveira and Hansen, 2008), T cell numbers in at term placenta's are low (Miyoshi et al, 2002). Therefore, we hypothesize that around parturition CD4 T cells, activated through indirect allorecognition of fetal MHC class I, activate uterine macrophages and induce a switch towards an inflammatory phenotype, characterized by the production of cytokines such as IL-1β, TNF-α and IL-8.…”

“…In humans reduced levels of regulatory T cells in the placenta and peripheral blood are associated with pre-eclampsia and preterm labor (Quinn and Parast, 2013) and depletion of regulatory T cells in allogeneic pregnancies in mice leads to failure of gestation (Aluvihare et al, 2004), showing the importance of regulatory T cells for successful pregnancy other species. Foxp3+ has been detected in the bovine placenta (Oliveira et al, 2013) and levels of CD4 CD25 T cells rise in peripheral blood of pregnant cows (Oliveira and Hansen, 2008).…”