Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies

TY - JOUR

T1 - Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies

AU - Blois, Sandra

AU - Tometten, Mareike

AU - Kandil, Judith

AU - Hagen, Evelin

AU - Klapp, Burghard F

AU - Margni, Ricardo A

AU - Arck, Petra C

PY - 2005/2/15

Y1 - 2005/2/15

N2 - Our understanding why a woman's immune system does not reject her histoincompatible fetus is still very limited. Distinct insights into the mechanisms involved in pregnancy maintenance may help us to prevent pregnancy complications, e.g., miscarriages or pre-eclampsia. Immune integration and tolerance at the feto-maternal interface appear to be indispensable for successful pregnancy maintenance. Little is known about the cross talk between ICAM-1, expressed on epithelium, endothelium, and APC, and its ligand, LFA-1, at the feto-maternal interface. However, based on the role of ICAM-1/LFA-1 in allograft acceptance or rejection upon transplantation, adhesion molecules are likely to interfere with successful pregnancy outcome. In this study, we tested the hypothesis that ICAM-1/LFA-1 pathways may be involved in pregnancy rejection in murine models. By blocking ICAM-1/LFA-1-mediated intercellular adhesion events, we show that fetal immune acceptance is restored in challenged pregnancies (e.g., upon exposure to sound stress), and adoptive transfer of LFA-1 cells into pregnant mice induces rejection only in abortion-prone mouse models. ICAM-1/LFA-1 cross talk leads to increased recruitment of proinflammatory cells to the implantation site, promotes dendritic cell maturation in the decidua, and subsequently induces additional local Th1 polarization via mature dendritic cells. Furthermore, our observations clearly point out that mechanisms of fetal tolerance, e.g., indoleamine 2,3-dioxygenase expression, presence of CD4+CD25bright regulatory T cells, and synthesis of asymmetric Abs, are ICAM-1/LFA-1 dependent. Hence, our data shed light on a hierarchical network of immune integration at the feto-maternal interface, in which ICAM-1/LFA-1 cross talk is clearly a proximate mediator capable of disrupting successful pregnancy maintenance.

AB - Our understanding why a woman's immune system does not reject her histoincompatible fetus is still very limited. Distinct insights into the mechanisms involved in pregnancy maintenance may help us to prevent pregnancy complications, e.g., miscarriages or pre-eclampsia. Immune integration and tolerance at the feto-maternal interface appear to be indispensable for successful pregnancy maintenance. Little is known about the cross talk between ICAM-1, expressed on epithelium, endothelium, and APC, and its ligand, LFA-1, at the feto-maternal interface. However, based on the role of ICAM-1/LFA-1 in allograft acceptance or rejection upon transplantation, adhesion molecules are likely to interfere with successful pregnancy outcome. In this study, we tested the hypothesis that ICAM-1/LFA-1 pathways may be involved in pregnancy rejection in murine models. By blocking ICAM-1/LFA-1-mediated intercellular adhesion events, we show that fetal immune acceptance is restored in challenged pregnancies (e.g., upon exposure to sound stress), and adoptive transfer of LFA-1 cells into pregnant mice induces rejection only in abortion-prone mouse models. ICAM-1/LFA-1 cross talk leads to increased recruitment of proinflammatory cells to the implantation site, promotes dendritic cell maturation in the decidua, and subsequently induces additional local Th1 polarization via mature dendritic cells. Furthermore, our observations clearly point out that mechanisms of fetal tolerance, e.g., indoleamine 2,3-dioxygenase expression, presence of CD4+CD25bright regulatory T cells, and synthesis of asymmetric Abs, are ICAM-1/LFA-1 dependent. Hence, our data shed light on a hierarchical network of immune integration at the feto-maternal interface, in which ICAM-1/LFA-1 cross talk is clearly a proximate mediator capable of disrupting successful pregnancy maintenance.

KW - Animals

KW - Antibodies, Blocking/pharmacology

KW - Cell Differentiation/immunology

KW - Cell Lineage/immunology

KW - Cell Movement/immunology

KW - Decidua/enzymology

KW - Dendritic Cells/cytology

KW - Female

KW - Graft Rejection/immunology

KW - Immune Tolerance/immunology

KW - Intercellular Adhesion Molecule-1/biosynthesis

KW - Lymphocyte Count

KW - Lymphocyte Function-Associated Antigen-1/biosynthesis

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred CBA

KW - Mice, Inbred DBA

KW - Pregnancy

KW - Pregnancy Proteins/antagonists & inhibitors

KW - Stress, Physiological/immunology

KW - Th1 Cells/cytology

KW - Th2 Cells/cytology

KW - Tryptophan Oxygenase/antagonists & inhibitors

KW - Up-Regulation/immunology

KW - Uterus/cytology

U2 - 10.4049/jimmunol.174.4.1820

DO - 10.4049/jimmunol.174.4.1820

M3 - SCORING: Journal article

C2 - 15699108

VL - 174

SP - 1820

EP - 1829

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 4

ER -