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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Apoptosis, Cell Death, Cytokines, Daclizumab, Fas Ligand Protein, Flow Cytometry, Heart Transplantation, Humans, Immunoglobulin G, Immunosuppressive Agents, Interleukin-2 Receptor alpha Subunit, Lymphocyte Activation, Membrane Glycoproteins, Myocardium, Receptors, Cytokine, Receptors, Interleukin, Receptors, Interleukin-2, Signal Transduction, T-Lymphocytes, fas Receptor.
user
Does anti-CD25 monoclonal antibody therapy affect the death signals of graft-infiltrating cells after clinical heart transplantation? Context: To define whether immunosuppressive agents that block the interleukin (IL)-2 pathway could prevent activation-induced cell death of activated T cells in the graft, we measured expression of IL-2, IL-2 receptor alpha chain (CD25), IL-15, Fas, and Fas ligand by real time reverse transcription-polymerase chain reaction in cardiac allografts. We characterized the phenotype of the infiltrating cells (CD3, CD68, CD25) by immunohistochemistry. The proportion of apoptotic graft-infiltrating cells was determined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. We analyzed endomyocardial biopsy specimens from cardiac allograft recipients who were treated with anti-CD25 monoclonal antibody (mAb) induction therapy (daclizumab) or with matching placebo in combination with cyclosporine, steroids, and mycophenolate mofetil. Treatment with anti-CD25 mAb affected the number of infiltrating CD3 and CD68 cells and the IL-2-regulated apoptotic pathway. During anti-CD25 mAb treatment, significantly lower intragraft IL-2 and CD25 mRNA transcription levels and decreased numbers of CD25+ T cells were found compared with the levels measured in endomyocardial biopsy specimens from placebo-treated patients (5- to 10-fold, P=0.002 and P<0.0001, respectively). In these samples the intragraft mRNA expression levels of IL-15 were also lower (P=0.02). Inhibition of the IL-2 pathway by anti-CD25 mAb therapy was accompanied by reduced mRNA and protein of Fas ligand and not by reduced Fas expression (P=0.001 and P=0.03). TUNEL staining revealed that the proportion of graft-infiltrating cells was lower in the anti-CD25 mAb patient group than the proportion of apoptotic cells in patients receiving placebo (P=0.06).
assistant
Our data suggest that immunosuppressive agents that affect the IL-2 pathway hinder the mechanism of activation-induced cell death by which the immune system eliminates alloreactive cells. Final Decision: yes