2. Academic Validation
  3. Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells

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

  • Sci Rep. 2015 Dec 16;5:18308. doi: 10.1038/srep18308.
Stephanie Vogel 1,  Elena Grabski 1,  Daniela Buschjäger 1,  Frank Klawonn 2 3,  Marius Döring 1,  Junxi Wang 3,  Erika Fletcher 4 5,  Ingo Bechmann 6,  Torsten Witte 7,  Martin Durisin 8,  Burkhart Schraven 9 10,  Sara M Mangsbo 4 5,  Kurt Schönfeld 11,  Niklas Czeloth 11,  Ulrich Kalinke 1
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Computer Science, Ostfalia University of Applied Sciences, Salzdahlumer Straße 46/48, D38302 Wolfenbüttel, Germany.
  • 3 Biostatistics, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D38124 Braunschweig, Germany.
  • 4 Department of Immunology Genetics and Pathology, Uppsala University, Rudbeck Laboratory, S75185 Uppsala, Sweden.
  • 5 Immuneed AB, S-756 52, Uppsala, Sweden.
  • 6 Institute for Anatomy, University Leipzig, Liebigstraße 13, D04103 Leipzig.
  • 7 Clinic for Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Straße 1, D30625 Hannover, Germany.
  • 8 Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Straße 1, D30625 Hannover, Germany.
  • 9 Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, D39120 Magdeburg, Germany.
  • 10 Department of Immune Control, Helmholtz Centre for Infection Research, Inhoffenstrß2 7, D38124 Braunschweig, Germany.
  • 11 Biotest AG, Dreieich, Landsteinerstrasse 5, D63303 Dreieich, Germany.
PMID: 26670584 DOI: 10.1038/srep18308
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.

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