Pregnancy is an immunological enigma where paternal antigens are present at the fetomaternal interface. What regulates the local immunotolerance, which is necessary to prevent rejection of the conceptus, is still under strong investigation. Gamma/delta T cells are believed to play a role in the local regulation of this immunotolerance towards the semiallogenic fetus. Gamma/delta T cells from the uterus and spleen of pregnant and nonpregnant mice were analyzed by flow cytometry. We confirmed that the rate of T cells in the decidua increases during murine pregnancy and half of decidual T cells are CD4+. Furthermore, we found a unique association of CD4 or CD8 coreceptor expression with their TCR intensity, where in all investigated groups CD4- or CD8-positive T cells seemed principally to be TCRdim. In addition, compared to peripheral T lymphocytes, a greater proportion of decidual T cells expressed the cytotoxic marker CD107a and markers of Th1 or Th2 polarization (TIM-3, TIM-1), where decidual TCRbright cells were characterized by high TIM-3 and TIM-1 receptor expression. On the other hand, no difference in the expression of CD160, a receptor with dual function affecting cytotoxicity and T cell inhibition, was detected. Within lymphocytes expressing CD107a, TIM-1, or CD160, the rate of T cells was significantly higher in the decidua. According to our results, cytotoxic potential of decidual TCRbright cells could be regulated by TIM-3 ligation, while the TIM-1 receptor seems to be able to influence the Th1-Th2 balance at the fetomaternal interface. These mechanisms could play a part in the active maternal immunotolerance towards the fetus, allowing an efficient protection against pathogens during healthy murine pregnancy.
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http://dx.doi.org/10.1155/2019/3836942 | DOI Listing |
Clin Exp Immunol
September 2024
Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Members of the T-cell immunoglobulin and mucin (TIM) family, which is crucial for T-cell function, are implicated in autoimmunity. TIM-1 and -3 play distinct roles in autoimmunity, with TIM-1 acting as a costimulatory molecule and TIM-3 regulating Th1 responses. We investigated the therapeutic potential of anti-TIM-1 (RMT1-10) and anti-TIM-3 (RMT3-23) antibodies in an autoimmune arthritis model.
View Article and Find Full Text PDFImmunohorizons
March 2024
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
J Immunother Cancer
December 2023
Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands
Background: CD1d is a monomorphic major histocompatibility complex class I-like molecule that presents lipid antigens to distinct T-cell subsets and can be expressed by various malignancies. Antibody-mediated targeting of CD1d on multiple myeloma cells was reported to induce apoptosis and could therefore constitute a novel therapeutic approach.
Methods: To determine how a CD1d-specific single-domain antibody (VHH) enhances binding of the early apoptosis marker annexin V to CD1d tumor cells we use in vitro cell-based assays and CRISPR-Cas9-mediated gene editing, and to determine the structure of the VHH1D17-CD1d(endogenous lipid) complex we use X-ray crystallography.
Nat Commun
October 2023
Department of Chemistry, Yale University, New Haven, CT, 06511, USA.
Mucin-domain glycoproteins are densely O-glycosylated and play critical roles in a host of biological functions. In particular, the T cell immunoglobulin and mucin-domain containing family of proteins (TIM-1, -3, -4) decorate immune cells and act as key regulators in cellular immunity. However, their dense O-glycosylation remains enigmatic, primarily due to the challenges associated with studying mucin domains.
View Article and Find Full Text PDFNature
July 2023
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
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