title: Lentiviral gene transfer of CTLA4 generates B cells with reduced costimulatory properties.
abstract: Peripheral T-cell (TC) tolerance can be induced by tolerogenic antigen-presenting cell (APC). A prerequisite is the reduction or blockade of B7 of APC. Besides dendritic cell, B cells can be used as APC. Here, we show the generation B cells with reduced B7 expression by lentiviral transduction of endoplasmic reticulum (ER)-directed CTLA4. Vectors coding for the human CTL4-Ig were used for the human B-cell line Raji. Transduction efficiency was over 90% (MOI = 3). For the murine B-cell line A20 and for primary mouse B cells, murine CTLA4 was used. We show that B cells with reduced B7 expression reduce the antigen (Ag) specific TC proliferation in vitro. B cells expressing an ER-directed CTLA4 may reduce Ag-specific immune responses.
authors.affiliation: Genethor GmbH, Goltz Strasse 52, 10781, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Vogt
authors.forename: M
authors.initials: M
authors.lastname: Warncke
authors.forename: B
authors.initials: B
authors.lastname: Micheel
authors.forename: A
authors.initials: A
authors.lastname: Sheriff
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse