Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation
Targeting CD100 by antibody blockade is a potential therapeutic strategy for cancers, but the functional effects on T cells following blockade of this immune activating molecule are rarely considered. Indeed, CD100 is highly expressed in T cells and anti-CD100 antibodies play a role during T cell pr...
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doaj-b87fde098eac46e28c8013494847afa92020-11-24T21:25:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00765268179Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell ProliferationXiaojun Jiang0Xiaojun Jiang1Xiaojun Jiang2Xiaojun Jiang3Niklas K. Björkström4Espen Melum5Espen Melum6Espen Melum7Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, NorwayFaculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, NorwayK.G. Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenNorwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, NorwayResearch Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, NorwayK.G. Jebsen Inflammation Research Centre, Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayTargeting CD100 by antibody blockade is a potential therapeutic strategy for cancers, but the functional effects on T cells following blockade of this immune activating molecule are rarely considered. Indeed, CD100 is highly expressed in T cells and anti-CD100 antibodies play a role during T cell proliferation; however, the outcome varies from different studies and the underlying mechanism is still unclear. To address this, monoclonal antibody clones directed against CD100 were evaluated. In their soluble form, four of these antibodies significantly reduced the expansion of T cells in the presence of bead-bound anti-CD3/CD28, either in total peripheral blood mononuclear cell or purified T cell culture systems. Similar inhibition was seen when blocking CD100–CD72 interaction by soluble anti-CD72 instead of anti-CD100 antibodies. Conversely, restoring the interaction by CD72-Fc eliminated the soluble anti-CD100-induced inhibitory effect. Taken together, these results reveal that T cell proliferation is regulated by CD100 via interaction with CD72. They further establish an in vitro system to evaluate the inhibitory effect of anti-CD100 antibodies on T cells, to which attention should be paid in clinical trials in order to avoid potential side effects.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00765/fullsemaphorin-4D/CD100CD72T cell proliferationantibody blockadesoluble anti-CD100 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Niklas K. Björkström Espen Melum Espen Melum Espen Melum |
spellingShingle |
Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Niklas K. Björkström Espen Melum Espen Melum Espen Melum Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation Frontiers in Immunology semaphorin-4D/CD100 CD72 T cell proliferation antibody blockade soluble anti-CD100 |
author_facet |
Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Xiaojun Jiang Niklas K. Björkström Espen Melum Espen Melum Espen Melum |
author_sort |
Xiaojun Jiang |
title |
Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation |
title_short |
Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation |
title_full |
Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation |
title_fullStr |
Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation |
title_full_unstemmed |
Intact CD100–CD72 Interaction Necessary for TCR-Induced T Cell Proliferation |
title_sort |
intact cd100–cd72 interaction necessary for tcr-induced t cell proliferation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-06-01 |
description |
Targeting CD100 by antibody blockade is a potential therapeutic strategy for cancers, but the functional effects on T cells following blockade of this immune activating molecule are rarely considered. Indeed, CD100 is highly expressed in T cells and anti-CD100 antibodies play a role during T cell proliferation; however, the outcome varies from different studies and the underlying mechanism is still unclear. To address this, monoclonal antibody clones directed against CD100 were evaluated. In their soluble form, four of these antibodies significantly reduced the expansion of T cells in the presence of bead-bound anti-CD3/CD28, either in total peripheral blood mononuclear cell or purified T cell culture systems. Similar inhibition was seen when blocking CD100–CD72 interaction by soluble anti-CD72 instead of anti-CD100 antibodies. Conversely, restoring the interaction by CD72-Fc eliminated the soluble anti-CD100-induced inhibitory effect. Taken together, these results reveal that T cell proliferation is regulated by CD100 via interaction with CD72. They further establish an in vitro system to evaluate the inhibitory effect of anti-CD100 antibodies on T cells, to which attention should be paid in clinical trials in order to avoid potential side effects. |
topic |
semaphorin-4D/CD100 CD72 T cell proliferation antibody blockade soluble anti-CD100 |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00765/full |
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