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Small Molecule Cyclotriazadisulfonamide Abrogates the Upregulation of the Human Receptors CD4 and 4-1BB and Suppresses In Vitro Activation and Proliferation of T Lymphocytes.
Front Immunol
September 2021
KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, Leuven, Belgium.
The small molecule cyclotriazadisulfonamide (CADA) down-modulates the human CD4 receptor, an important factor in T cell activation. Here, we addressed the immunosuppressive potential of CADA using different activation models. CADA inhibited lymphocyte proliferation with low cellular toxicity in a mixed lymphocyte reaction, and when human PBMCs were stimulated with CD3/CD28 beads, phytohemagglutinin or anti-CD3 antibodies.
View Article and Find Full Text PDFA novel approach to measuring cell-mediated lympholysis using quantitative flow and imaging cytometry.
J Immunol Methods
December 2015
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. Electronic address:
In this study, we established a novel isotope-free approach for the detection of cell-mediated lympholysis (CML) in MHC defined peripheral blood mononuclear cells (PBMCs) using multiparameter flow and imaging cytometry. CML is an established in vitro assay to detect the presence of cytotoxic effector T-lymphocytes precursors (CTLp). Current methods employed in the identification of CTLp in the context of transplantation are based upon the quantification of chromium ((51)Cr) released from target cells.
View Article and Find Full Text PDFEffects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.
Am J Transplant
March 2016
Center for Transplantation Science, Department of Surgery, Massachusetts General Hospital, Boston, MA.
A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days.
View Article and Find Full Text PDFRole of innate and acquired immune mechanisms in clinical intestinal transplant rejection.
Transplantation
June 2015
1 Department of Surgery, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL. 2 Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL. 3 Jesse Brown VA Medical Center, Chicago, IL. 4 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 5 Department of Microbiology-Immunology, University of Miami Miller School of Medicine, Miami, FL. 6 Miami VA Medical Center, Miami, FL. 7 Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Background: Long-term outcomes of intestinal transplantation are limited by infection and rejection. To understand the underlying immune mechanisms, graft infiltrating and peripheral blood cells were analyzed using multiple ex vivo assays in intestinal transplantation recipients.
Methods: Infiltrating cells from rejected (graft enterectomy for rejection) and accepted or quiescent (stoma closure in stable transplant recipients) grafts were isolated and phenotypically characterized as to subsets and Toll-like receptor expressions as well as functionally tested for antimicrobial and antidonor immune responses.
Assessment of anti-donor T cell proliferation and cytotoxic T lymphocyte-mediated lympholysis in living donor kidney transplant patients.
Methods Mol Biol
May 2015
Department of Translational and Regenerative Medicine, Research Block B, 5th Floor, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, India,
Organ transplant recipients are at risk of allograft rejection, and remain dependent on lifelong immunosuppressive agents, with the attendant risks of infections, cancers, and drug toxicities. Mesenchymal stromal cells (MSCs) have emerged as an alternative to the current pharmacologic immunosuppressive therapy as these cells are immune privileged and possess immunomodulatory properties. However, clinical data are incomplete regarding the efficacy of MSC therapy to control alloimmune response of the transplant recipients.
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