Enhancement of megakaryocytopoiesis by Campath-1G-treated natural killer cells

• Published in: Bone marrow transplantation (Basingstoke) Vol. 20; no. 7; pp. 525 - 531
• Main Authors: NAGLER, A, CONDIOTTI, R, LUBINA, A, DEUTSCH, V. R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.10.1997
• Subjects: Alemtuzumab; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antibodies; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antigens, CD - immunology; Antigens, Neoplasm; Autografts; Biocompatibility; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; CD16 antigen; CD52 Antigen; Cell activation; Cell Differentiation; Cell proliferation; Cells, Cultured; Coculture Techniques; Colonies; Colony-stimulating factor; Cytokines; Cytotoxicity; Dogs; Glycoproteins; Graft-versus-host reaction; Hematopoiesis; Humans; Immunoglobulin G; Immunomodulation; Immunosuppressive Agents - immunology; Immunosuppressive Agents - pharmacology; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Medical sciences; Megakaryocytes - cytology; Megakaryocytes - immunology; Natural killer cells; Peripheral blood mononuclear cells; Stem cell transplantation; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Immunopathology; Megakaryocytopoiesis; Targeting; Immunomodulation; Homograft; Cytotoxicity; Graft versus host reaction; Monoclonal antibody; Biological activity; Natural killer cell; Prevention; Immunotherapy; T-Lymphocyte; Bone marrow; Graft
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1700952

Campath-1G is a CD52 (rat IgG2b) moAb used in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD) by the elimination of T cells via antibody-dependent cell cytotoxicity (ADCC) in vivo. We have previously reported that Campath-1G induces T cell proliferation, activation, and production of cytokines which in turn causes an enhancement of megakaryocytopoiesis in vitro. In view of the fact that recent studies have indicated that natural killer (NK) cells may also be involved in the regulation of megakaryocytopoiesis, we undertook the study of the in vitro effect of Campath-1G-treated NK cells on the regulation of megakaryocytopoiesis. Early burst-forming BFU-MK and late colony-forming CFU-MK were grown from 2 x 10(5) peripheral blood non-adherent mononuclear cells (NAMC) in plasma clots in the presence of aplastic canine plasma (PICS-J) which was used as megakaryocyte colony-stimulating factor (MK-CSF). The first step in elucidating this series of events was to investigate the direct influence of NK cells on megakaryocytopoiesis. Co-culturing NK cells (>85% CD16+) with autologous NAMC at a ratio of 1:1 resulted in a significant increase in the proliferation of CFU-MK and BFU-MK over NAMC cultured alone. This effect was further enhanced upon exposure of NK to Campath-1G (0.1-3 microg/ml). To investigate the possible influence of soluble factors released from NK cells treated with Campath-1G on MK maturation, conditioned medium (CM) derived from Campath-1G-treated-enriched populations of NK cells was found to enhance MK progenitor growth. Our data demonstrate that resting and Campath-1G-treated NK may be involved in the immunomodulation of megakaryocytopoiesis.