Infertility and subfertility reduce the economic viability of dairy production. Early pregnancy involves transient secretion of a unique type I interferon, interferon tau (IFNT). Our working hypothesis is that pregnancy induces changes in immune cells that are biased toward tolerance, tissue remodeling and angiogenesis. Early pregnancy is accompanied by a marked increase in the proportion of endometrial CD45+ cells expressing markers for natural killer (NK) cells and cytotoxic T cells (CD8) and an increase in MHCII+ cells, particularly around shallow glands of the endometrium of pregnant heifers at Day 20. This is accompanied by increased abundance of mRNA for interleukin (IL)-15, an NK growth factor, and IL-10, a tolerogenic cytokine, in the endometrium during early pregnancy. Furthermore, expression of indoleamine 2,3 dioxygenase (IDO) was 15-fold greater in pregnant compared with cyclic heifers at Day 17, but then declined by Day 20 of pregnancy to amounts similar to Day 17 cyclic heifers. IDO converts tryptophan to kynurenine, which is thought to alter immune function by activation of the aryl hydrocarbon receptor (AHR) and induction of tolerogenic mediators. Interestingly, AHR protein expression is greater in the endometrium during this same period. Pregnancy is also associated with increased expression of inhibitory proteins programed death ligand-1, lymphocyte activation gene-3 and cytotoxic T-lymphocyte associated protein-4. These molecules interact with receptors on antigen-presenting cells and induce lymphocyte tolerance. Expression of IDO, IL10 and other immune cell regulators were greater in pregnant compared with cyclic heifers but then decreased between Day 17 and 20 of pregnancy. We interpret this to indicate that early pregnancy signaling in dairy heifers involves immune cell activation including increased lymphoid and myeloid lineage cells as well as induction of molecules known to mediate tolerance. Early pregnancy is accompanied by induction and then repression of mediators of immune function, which may serve as a developmental switch to promote immune privileged niche and tissue remodeling in the endometrium. Supported in part by Agriculture and Food Research Initiative Competitive Grant 2017-67015-26455 from the USDA National Institute of Food and Agriculture.