title: CD52 ligation induces CD4 and CD8 down modulation in vivo and in vitro.
abstract: To successfully induce donor-specific tolerance after immune depletion, it is essential to understand the residual and recovering immune system in the context of the depleting agent because the properties of such a recovering immune system differ based on the depleting agent used. In this study, we investigate the phenotypic and functional characteristics of T cells exposed to Campath-1H in vivo and in vitro. Recovering T cells demonstrated down modulated surface CD4 and CD8 (by flow cytometry) for up to 45 days after Campath-1H administration. Additionally, these T cells had an activated phenotype. To determine whether this CD4/8 down modulation was due to T-cell activation only or in part due to Campath-1H, whole blood from healthy volunteers was exposed to Campath-1H and the surviving lymphocytes isolated. Flow cytometry revealed a dose-dependent down modulation of CD4/8 without T-cell activation. Additionally, these Campath-1H-treated T cells were immunocompetent as indicated by increased surface CD69 and interleukin-2 (IL-2) production following stimulation by soluble anti-CD3 mAb. In conclusion, Campath-1H by itself down modulates surface CD4 and CD8 without activating T cells.
authors.affiliation: Department of Surgery, Division of Transplantation Surgery and Immunology, University of Vermont, Burlington, VT 05405-0068, USA.
authors.forename: Akeesha
authors.initials: A
authors.lastname: Shah
authors.forename: Hayden
authors.initials: H
authors.lastname: Lowenstein
authors.forename: Alan
authors.initials: A
authors.lastname: Chant
authors.forename: Abrar
authors.initials: A
authors.lastname: Khan
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000074301:CD52 Antigen; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D000074301:CD52 Antigen; D016827:CD8 Antigens; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D037181:Lectins, C-Type; D008024:Ligands; D000099192:CD69 Antigens; C000613862:CD52 protein, human