The Interleukin-2 Receptor α Chain (CD25) Plays an Important Role in Regulating Monocyte-Derived CD40 Expression During Anti-Porcine Cellular Responses

• Published in: Transplantation proceedings Vol. 44; no. 4; pp. 1139 - 1142
• Main Authors: Sun, Z.-G, Wang, Z, Zhu, L.-M, Fang, Y.-S, Yu, L.-Z, Xu, H
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2012; Elsevier
• Subjects: Animals; Antibodies, Monoclonal, Humanized - pharmacology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens - metabolism; Cell Communication - drug effects; Cell Proliferation; Cells, Cultured; Coculture Techniques; Endothelial Cells - immunology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Humans; Immunoglobulin G - pharmacology; Interferon-gamma - metabolism; Interleukin-2 Receptor alpha Subunit - antagonists & inhibitors; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Lipopolysaccharide Receptors - metabolism; Lymphocyte Activation; Medical sciences; Monocytes - drug effects; Monocytes - immunology; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Swine; Time Factors; Tissue, organ and graft immunology; Transplantation, Heterologous; Up-Regulation; Monocyte; Cellular immunity; Transplantation; Gene expression; Pig; Medicine; Play; Vertebrata; Mammalia; Treatment; Interleukin 2 receptor; Surgery; Animal; Alpha-Peptide chain; Graft; Artiodactyla; Ungulata
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2012.02.014

Abstract Long-term xenograft survival is limited by delayed xenograft rejection, and monocytes are thought to play an important role in this process. Although typically considered a T cell surface marker, interleukin 2 the receptor chain CD25 is also functional on monocytes. We hypothesized that CD25 expression on monocytes functions to augment monocyte activation in xeno-specific cellular responses. Xenogeneic mixed lymphocyte-endothelial cell reactions were used to study the role of CD25 in facilitating xenogeneic cell-mediated immune responses an in vitro. We also tested the effect of the anti-CD25 antibody daclizumab on monocyte-mediated T cell activation during xeno-specific cellular responses. Co-culture with porcine endothelial cells (PEC) elicited a pronounced proliferative response by human peripheral blood mononuclear cells (PBMC) that was accompanied by upregulation of CD25 and CD40 on CD14+ monocytes. CD4+ cells proliferated in response to PEC-conditioned monocytes, while blockade of CD25 with daclizumab reduced CD4+ cell proliferation in the presence of PEC-conditioned monocytes. In addition, daclizumab inhibited proliferation of PBMC in responses to PEC. Analysis of monocytes from PBMC-PEC cocultures by flow cytometry indicated that daclizumab inhibited CD40 upregulation on PEC-activated monocytes. These data demonstrate that CD25 blockade prevents xenogeneic cellular responses by directly blocking CD25 expression on both activated T cells and monocytes. CD25 blockade on T cells or monocytes may indirectly affect upregulation of CD40 on xenoreactive monocytes. Our data strengthen the rationale for incorporating CD25 directed therapy in discordant xenotransplantation.