Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells

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...

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Main Authors:	Vogel, Stephanie, Grabski, Elena, Buschjäger, Daniela, Klawonn, Frank, Döring, Marius, Wang, Junxi, Fletcher, Erika, Bechmann, Ingo, Witte, Torsten, Durisin, Martin, Schraven, Burkhart, Mangsbo, Sara M., Schönfeld, Kurt, Czeloth, Niklas, Kalinke, Ulrich
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680940/

id	pubmed-4680940
recordtype	oai_dc
spelling	pubmed-46809402015-12-18 Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells Vogel, Stephanie Grabski, Elena Buschjäger, Daniela Klawonn, Frank Döring, Marius Wang, Junxi Fletcher, Erika Bechmann, Ingo Witte, Torsten Durisin, Martin Schraven, Burkhart Mangsbo, Sara M. Schönfeld, Kurt Czeloth, Niklas Kalinke, Ulrich Article 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. Nature Publishing Group 2015-12-16 /pmc/articles/PMC4680940/ /pubmed/26670584 http://dx.doi.org/10.1038/srep18308 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Vogel, Stephanie Grabski, Elena Buschjäger, Daniela Klawonn, Frank Döring, Marius Wang, Junxi Fletcher, Erika Bechmann, Ingo Witte, Torsten Durisin, Martin Schraven, Burkhart Mangsbo, Sara M. Schönfeld, Kurt Czeloth, Niklas Kalinke, Ulrich
spellingShingle	Vogel, Stephanie Grabski, Elena Buschjäger, Daniela Klawonn, Frank Döring, Marius Wang, Junxi Fletcher, Erika Bechmann, Ingo Witte, Torsten Durisin, Martin Schraven, Burkhart Mangsbo, Sara M. Schönfeld, Kurt Czeloth, Niklas Kalinke, Ulrich Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
author_facet	Vogel, Stephanie Grabski, Elena Buschjäger, Daniela Klawonn, Frank Döring, Marius Wang, Junxi Fletcher, Erika Bechmann, Ingo Witte, Torsten Durisin, Martin Schraven, Burkhart Mangsbo, Sara M. Schönfeld, Kurt Czeloth, Niklas Kalinke, Ulrich
author_sort	Vogel, Stephanie
title	Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
title_short	Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
title_full	Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
title_fullStr	Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
title_full_unstemmed	Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells
title_sort	antibody induced cd4 down-modulation of t cells is site-specifically mediated by cd64+ cells
description	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.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680940/
_version_	1613513296866967552

Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64+ cells

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