title: Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells.
abstract: Treatment of PBMC with the CD4-specific mAb BT-061 induces CD4 down-modulation of T cells. Here we report that addition of BT-061 to purified T cells did not confer this effect, whereas incubation of T cells in BT-061 coated wells restored CD4 down-modulation. These results implied that Fcγ receptor mediated cell-cell interactions played a role. In consistence with this hypothesis PBMC depleted of CD64(+) monocytes did not confer CD4 down-modulation of BT-061 decorated T cells. Strikingly, CD4 down-modulation was observed in BT-061 treated synovial fluid punctuated from patients' inflamed joints that comprised enhanced numbers of CD64(+) cells. In contrast, in a circulating whole blood system injection of BT-061 did not induce CD4 down-modulation, due to CD64 saturation by serum IgG. Similarly, tonsil derived mononuclear cells devoid of CD64(+) cells did not show CD4 down-modulation, whereas addition of blood derived monocytes restored the effect. Thus, the interaction of BT-061 decorated T cells with CD64(+) cells is needed for CD4 down-modulation, implying that in patients BT-061 would primarily induce CD4 down-modulation at inflammatory sites. These results highlight the need not only to examine the interaction of a given mAb with single FcγR, but also the immunological environment that is appropriate to support such interactions.
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Feodor-Lynen-Straße 7, D30625 Hannover.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Vogel
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Feodor-Lynen-Straße 7, D30625 Hannover.
authors.forename: Elena
authors.initials: E
authors.lastname: Grabski
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Feodor-Lynen-Straße 7, D30625 Hannover.
authors.forename: Daniela
authors.initials: D
authors.lastname: Buschjäger
authors.affiliation: Department of Computer Science, Ostfalia University of Applied Sciences, Salzdahlumer Straße 46/48, D38302 Wolfenbüttel, Germany.|Biostatistics, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D38124 Braunschweig, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Feodor-Lynen-Straße 7, D30625 Hannover.
authors.forename: Marius
authors.initials: M
authors.lastname: Döring
authors.affiliation: Biostatistics, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D38124 Braunschweig, Germany.
authors.forename: Junxi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Immunology Genetics and Pathology, Uppsala University, Rudbeck Laboratory, S75185 Uppsala, Sweden.|Immuneed AB, S-756 52, Uppsala, Sweden.
authors.forename: Erika
authors.initials: E
authors.lastname: Fletcher
authors.affiliation: Institute for Anatomy, University Leipzig, Liebigstraße 13, D04103 Leipzig.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.affiliation: Clinic for Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Straße 1, D30625 Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.affiliation: Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Straße 1, D30625 Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Durisin
authors.affiliation: Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, D39120 Magdeburg, Germany.|Department of Immune Control, Helmholtz Centre for Infection Research, Inhoffenstrß2 7, D38124 Braunschweig, Germany.
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.affiliation: Department of Immunology Genetics and Pathology, Uppsala University, Rudbeck Laboratory, S75185 Uppsala, Sweden.|Immuneed AB, S-756 52, Uppsala, Sweden.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Mangsbo
authors.affiliation: Biotest AG, Dreieich, Landsteinerstrasse 5, D63303 Dreieich, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Schönfeld
authors.affiliation: Biotest AG, Dreieich, Landsteinerstrasse 5, D63303 Dreieich, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Czeloth
authors.affiliation: Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Feodor-Lynen-Straße 7, D30625 Hannover.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke