title: Early Differentiation of Human CD11c+NK Cells withγδT Cell Activation Properties Is Promoted by Dialyzable Leukocyte Extracts.
abstract: Reconstitution of the hematopoietic system during immune responses and immunological and neoplastic diseases or upon transplantation depends on the emergent differentiation of hematopoietic stem/progenitor cells within the bone marrow. Although in the last decade the use of dialyzable leukocyte extracts (DLE) as supportive therapy in both infectious and malignant settings has increased, its activity on the earliest stages of human hematopoietic development remains poorly understood. Here, we have examined the ability of DLE to promote replenishment of functional lymphoid lineages from CD34+cells. Our findings suggest that DLE increases their differentiation toward a conspicuous CD56+CD16+CD11c+NK-like cell population endowed with properties such as IFNy production, tumor cell cytotoxicity, and the capability of inducingγδT lymphocyte proliferation. Of note, long-term coculture controlled systems showed the bystander effect of DLE-stromal cells by providing NK progenitors with signals to overproduce this cell subset. Thus, by direct effect on progenitor cells and through activation and remodeling of the supporting hematopoietic microenvironment, DLE may contribute a robust innate immune response by promoting the emerging lymphopoiesis of functional CD11c+NK cells in a partially TLR-related manner. Unraveling the identity and mechanisms of the involved DLE components may be fundamental to advance the NK cell-based therapy field.
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenida Cuauhtémoc 330, Colonia Doctores, 06720 Mexico City, Mexico; Department of Immunology, National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico.
authors.forename: Dalia
authors.initials: D
authors.lastname: Ramírez-Ramírez
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenida Cuauhtémoc 330, Colonia Doctores, 06720 Mexico City, Mexico.
authors.forename: Eduardo
authors.identifier: 0000-0001-5939-8031
authors.initials: E
authors.lastname: Vadillo
authors.affiliation: Immunochemistry Research Unit, Medical Specialties Hospital, Mexican Institute for Social Security, Avenida Cuauhtémoc 330, Colonia Doctores, 06720 Mexico City, Mexico.
authors.forename: Lourdes Andrea
authors.initials: LA
authors.lastname: Arriaga-Pizano
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenida Cuauhtémoc 330, Colonia Doctores, 06720 Mexico City, Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Mayani
authors.affiliation: Department of Immunology, National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico; Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico; Unidad de Investigación, Desarrollo e Innovación Médica y Biotecnológica (UDIMEB), National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.affiliation: Department of Pharmacology, School of Medicine, National Autonomous University of Mexico, Ciudad Universitaria, 04510 Mexico City, Mexico.
authors.forename: Marco Antonio
authors.identifier: 0000-0001-9717-0265
authors.initials: MA
authors.lastname: Velasco-Velázquez
authors.affiliation: Department of Immunology, National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico; Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico; Unidad de Investigación, Desarrollo e Innovación Médica y Biotecnológica (UDIMEB), National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Carpio y Plan de Ayala s/n, Colonia Santo Tomás, 11340 Mexico City, Mexico.
authors.forename: Sonia Mayra
authors.identifier: 0000-0002-2818-8522
authors.initials: SM
authors.lastname: Pérez-Tapia
authors.affiliation: Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenida Cuauhtémoc 330, Colonia Doctores, 06720 Mexico City, Mexico.
authors.forename: Rosana
authors.identifier: 0000-0003-3401-9757
authors.initials: R
authors.lastname: Pelayo
mesh_terms: D039521:CD11c Antigen / Q000032:analysis; D002478:Cells, Cultured; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017154:Stromal Cells / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D014165:Transfer Factor / Q000494:pharmacology*
chemical_list: D039521:CD11c Antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014165:Transfer Factor; D007371:Interferon-gamma