title: The interleukin-2 receptor α chain (CD25) plays an important role in regulating monocyte-derived CD40 expression during anti-porcine cellular responses.
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.
authors.affiliation: Department of Thoracic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Sun
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: L-M
authors.initials: LM
authors.lastname: Zhu
authors.forename: Y-S
authors.initials: YS
authors.lastname: Fang
authors.forename: L-Z
authors.initials: LZ
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D000077561:Daclizumab; D042783:Endothelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D019013:CD40 Antigens; C508017:IL2RA protein, human; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; D018950:Lipopolysaccharide Receptors; D007371:Interferon-gamma; D000077561:Daclizumab