Evidence that CD8 T‐cell homeostasis and function remain intact during murine pregnancy

Abstract

SummaryEvolving models of immune tolerance have challenged the view that the response of the maternal immune system to environmental or fetal antigens must be suppressed or deviated. CD8 T cells play a central role in the immune response to viruses and intracellular pathogens so the maintenance of both the number and function of these cells is critical to protect both the mother and fetus. We show that the numbers of maternal CD8 T cells in both the spleen and the uterine draining lymph nodes are transiently increased at mid-gestation and this correlates with enhanced CD8 T-cell proliferation and an increased relative expression of both prosurvival and pro-apoptotic molecules. In transgenic mice bearing T-cell antigen receptors specific for the male HY or allo-antigens, the transgenic CD8 T cells retain the ability to proliferate and function during pregnancy. Moreover, anti-HY T-cell receptor transgenic mice have normal numbers of male pups despite the presence of CD8 T cells at the maternal-fetal interface. These data suggest that pregnancy is a dynamic state in which CD8 T-cell turnover is increased while the function and ending size of the CD8 T-cell compartment are maintained.

Fetal-Specific CD8+ Cytotoxic T Cell Responses Develop during Normal Human Pregnancy and Exhibit Broad Functional Capacity

“…However, these data are in agreement with some studies in HY transgenic mice that demonstrated that the presence of such cells did not affect litter size even when the CD8 + T cells were found at the maternal/ fetal interface (22). This suggests that mechanisms other than deletion are critical factors enabling the fetus to escape from recognition by fetus-specific T cells.…”

“…This suggests that mechanisms other than deletion are critical factors enabling the fetus to escape from recognition by fetus-specific T cells. Downregulation of HLA expression on trophoblast and syncytiotrophoblast is one possible factor in this regard, although expression of HY Ag on these tissues did not affect pregnancy viability in a murine model (22). The functional potential of fetal-specific T cells was clear following in vitro expansion, but it is possible that in vivo, during healthy pregnancy, they remain in some way functionally attenuated or anergic.…”

“…An initial proliferation of fetal-specific T cells that are hyporesponsive to maternal tissue has been seen (17)(18)(19). Although some models demonstrate partial deletion of this fetal-specific response (17)(18)(19) through a process that may be Fas/Fas ligand-dependent (20), other reports have not documented deletion of fetal-specific T cells (21,22) or any evidence of loss of cellular function (22). Thus, whereas murine models have been valuable for developing insights into fetal-specific immunity during pregnancy, they are inconclusive and sometimes conflicting.…”

Impact of Immune Deficiency on Remodeling of Maternal Resistance Vasculature 4 Weeks Postpartum in Mice

“…This may have either changed their phenotype or selected a specialized subset of CD8 T cells not normally present in pregnant B6 mice. However, we have shown that pregnancy in normal mice supports turnover in the CD8 T-cell population, 21,22 and it is likely that such homeostatic turnover occurs similarly, but perhaps to a slightly greater extent in CD8 T cells transferred to Rag1 À/À mice and in CD8 T cells from normal B6 mice under the influence of pregnancy and PP.…”

“…[21][22][23][24] We have studied T-cell homeostasis in mice and observed changes in the maternal immune system that persist PP. [21][22][23][25][26][27] There may be accumulation of TREGs in PP that may protect subsequent pregnancies.…”