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Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells.
Vogel, Stephanie Grabski, Elena Buschjäger, Daniela Döring, Marius Wang, Junxi Fletcher, Erika Bechmann, Ingo Witte, Torsten Durisin, Martin
Vogel, Stephanie
Grabski, Elena
Buschjäger, Daniela
Döring, Marius
Wang, Junxi
Fletcher, Erika
Bechmann, Ingo
Witte, Torsten
Durisin, Martin
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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.
Citation
Antibody induced CD4 down-modulation of T cells is site-specifically mediated by CD64(+) cells. 2015, 5:18308 Sci Rep
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PubMed ID
PubMed Central ID
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Article
Language
en
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Series/Report no.
ISSN
2045-2322