title: Homing receptor expression is deviated on CD56+ blood lymphocytes during pregnancy in Type 1 diabetic women.
abstract: Type 1 Diabetes Mellitus (T1DM) is characterized by an augmented pro-inflammatory immune state. This contributes to the increased risk for gestational complications observed in T1DM mothers. In normal pregnancies, critical immunological changes occur, including the massive recruitment of lymphocytes, particularly CD56bright NK cells, into early decidua basalis and a 2nd trimester shift towards Type 2 immunity. Decidual CD56bright NK cells arise at least partly from circulating progenitors expressing adhesion molecules SELL and ITGA4 and the chemokine receptors CXCR3 and CXCR4. In vitro studies show that T1DM reduces interactions between blood CD56+ NK cells and decidual endothelial cells by reducing SELL and ITGA4-based interactions. To address the mechanisms by which specific lymphocyte subsets may be recruited from the circulation during pregnancy and whether these mechanisms are altered in T1DM, flow cytometry was used to examine eight peripheral blood lymphocyte subsets (Type 1 (IL18R1+) and Type 2 (IL1RL1+) CD56bright NK, CD56dim NK, NKT and T cells) from control and T1DM women. Blood was collected serially over pregnancy and postpartum, and lymphocytes were compared for expression of homing receptors SELL, ITGA4, CXCR3, and CXCR4. The decline of Type 1/Type 2 immune cells in normal pregnancy was driven by an increase in Type 2 cells that did not occur in T1DM. CD56bright NK cells from control women had the highest expression of all four receptors with greatest expression in 2nd trimester. At this time, these receptors were expressed at very low levels by CD56bright NK cells from TIDM patients. Type 1/Type 2 NKT cell ratios were not influenced by either pregnancy or TIDM. Our results suggest that T1DM alters immunological balances during pregnancy with its greatest impact on CD56bright NK cells. This implicates CD56bright NK cells in diabetic pregnancy complications.
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Suzanne D
authors: SD
authors: Burke
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Alexandra V C
authors: AV
authors: Seaward
authors: Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
authors: Heather
authors: H
authors: Ramshaw
authors: Department of Obstetrics and Gynecology, Queen's University, Kingston, Ontario, Canada.
authors: Graeme N
authors: GN
authors: Smith
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Sophia
authors: S
authors: Virani
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Barbara A
authors: BA
authors: Croy
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors: Patricia D A
authors: PD
authors: Lima
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D049590:Postpartum Period; D011247:Pregnancy; D016201:Receptors, Lymphocyte Homing / Q000235:genetics / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D019002:CD56 Antigen; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016201:Receptors, Lymphocyte Homing