title: Different mechanisms of Campath-1H-mediated depletion for CD4 and CD8 T cells in peripheral blood.
abstract: It is assumed that complement and noncomplement-mediated mechanisms are similarly responsible for Campath-1H-mediated killing of all T-cell subtypes in vivo. However, the differing surface expression of CD52 on T-cell subtypes suggests that may not be the case. The purpose of this study is to determine the extent and mechanism of Campath-1H-mediated elimination of different T-cell subtypes in peripheral blood. Whole blood or lymphocytes isolated from peripheral blood of healthy volunteers by Ficoll density centrifugation were incubated with Campath-1H, with or without complement and/or serum, and the resultant T-cell elimination mechanisms studied. For CD4(+) T lymphocytes, 60% and 40% cell death and for CD8(+) T lymphocytes 23% and 77% cell death, in peripheral blood, was mediated by complement and noncomplement mediated mechanisms, respectively. CD4(+) T cells demonstrated approximately twice the amount of surface CD52 compared with CD8(+) T cells, consistent with primarily complement-mediated killing for CD4(+) T cells. Thus, peripheral blood supports differential and partial elimination of T-cell subtypes, suggesting that the complete T-cell elimination seen in transplant recipients is most likely due to contribution from other lymphoid organs.
authors.affiliation: Department of Surgery, Division of Transplantation Surgery and Immunology, University of Vermont, Burlington, 05405-0068, USA.
authors.forename: Hayden
authors.initials: H
authors.lastname: Lowenstein
authors.forename: Akeesha
authors.initials: A
authors.lastname: Shah
authors.forename: Alan
authors.initials: A
authors.lastname: Chant
authors.forename: Abrar
authors.initials: A
authors.lastname: Khan
mesh_terms: D000074323:Alemtuzumab; D000643:Ammonium Chloride / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D000074301:CD52 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D016923:Cell Death; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D000643:Ammonium Chloride; D000074323:Alemtuzumab