PMID- 28633489 OWN - NLM STAT- MEDLINE DCOM- 20180510 LR - 20180510 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 97 IP - 1 DP - 2017 Jul 1 TI - Effects of early pregnancy on uterine lymphocytes and endometrial expression of immune-regulatory molecules in dairy heifers. PG - 104-118 LID - 10.1093/biolre/iox061 [doi] AB - Natural killer (NK) cells are essential for establishment of human and rodent pregnancies. The function of these and other cytotoxic T cells (CTL) is controlled by stimulatory and inhibitory signaling. A role for cytotoxic cells during early pregnancy in cattle has not been described, but regulation of their function at the fetal-maternal interface is thought to be critical for conceptus survival. The hypothesis that the relative abundance of CTL and expression of inhibitory signaling molecules is increased by the conceptus during early pregnancy was tested. The proportions of lymphoid lineage cells and expression of inhibitory signaling molecules in the endometrium during early pregnancy in dairy heifers were determined using flow cytometry, immunofluorescence, and real-time PCR on days 17 and 20 of pregnancy and day 17 of the estrous cycle. Results revealed an increased percentage of NKp46+ and CD8+ cells in the uterus of pregnant heifers. Furthermore, a large percentage of uterine immune cells coexpressed these proteins. Compared to cyclic heifers, CD45+ uterine cells from pregnant heifers exhibited greater degranulation. Endometrium from pregnant heifers had greater mRNA abundance for the inhibitory molecules, CD274 and lymphocyte activating gene 3 (LAG3), and greater cytotoxic T lymphocyte-associated protein 4 (CTLA4), molecules that can interact with receptors on antigen-presenting cells and induce lymphocyte tolerance. This study demonstrates a dynamic regulation of both cytotoxic immune cells and tolerogenic molecules during the peri-implantation period that may be required to support establishment of pregnancy and placentation. CI - (c) The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Vasudevan, Sreelakshmi AU - Vasudevan S AD - Department of Animal Science, Center for Reproductive Biology and Health, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. AD - VA Medical Center, San Francisco, California, USA. FAU - Kamat, Manasi M AU - Kamat MM AD - Department of Animal Science, Center for Reproductive Biology and Health, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. AD - City of Hope, Duarte, California, USA. FAU - Walusimbi, Sadhat S AU - Walusimbi SS AD - Department of Animal Science, Center for Reproductive Biology and Health, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. AD - Department of Agricultural Production, School of Agricultural Sciences, College of Agricultural and Environmental Sciences, Makerere University, Kampala, Uganda. FAU - Pate, Joy L AU - Pate JL AD - Department of Animal Science, Center for Reproductive Biology and Health, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. FAU - Ott, Troy L AU - Ott TL AD - Department of Animal Science, Center for Reproductive Biology and Health, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania, USA. LA - eng PT - Journal Article PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cattle MH - Female MH - Gene Expression Regulation/*immunology MH - Interferon-gamma/genetics/metabolism MH - Interleukin-10/genetics/metabolism MH - Killer Cells, Natural MH - Lymphocytes/*physiology MH - Pregnancy MH - *Pregnancy, Animal/physiology MH - Uterus/*cytology/metabolism OTO - NOTNLM OT - cattle OT - cytotoxic T cells OT - endometrium OT - natural killer cells OT - pregnancy EDAT- 2017/06/22 06:00 MHDA- 2018/05/11 06:00 CRDT- 2017/06/22 06:00 PHST- 2017/05/30 00:00 [received] PHST- 2017/06/15 00:00 [accepted] PHST- 2017/06/22 06:00 [pubmed] PHST- 2018/05/11 06:00 [medline] PHST- 2017/06/22 06:00 [entrez] AID - 3869920 [pii] AID - 10.1093/biolre/iox061 [doi] PST - ppublish SO - Biol Reprod. 2017 Jul 1;97(1):104-118. doi: 10.1093/biolre/iox061.