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B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction
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Leitner, Judith, Klauser, Christoph, Pickl, Winfried F., Stöckl, Johannes, Majdic, Otto, Bardet, Anaïs F., Kreil, David, Dong, Chen, Yamazaki, Tomohide, Zlabinger, Gerhard, Pfistershammer, Katharina and Steinberger, Peter (2009) B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction. European Journal of Immunology, Vol.39 (No.7). pp. 1754-1764. doi:10.1002/eji.200839028 ISSN 0014-2980.
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Official URL: http://dx.doi.org/10.1002/eji.200839028
Abstract
B7-H3 belongs to the B7 superfamily, a group of molecules that costimulate or down-modulate T-cell responses. Although it was shown that B7-H3 could inhibit T-cell responses, several studies – most of them performed in murine systems – found B7-H3 to act in a costimulatory manner. In this study, we have specifically addressed a potential functional dualism of human B7-H3 by assessing the effect of this molecule under varying experimental conditions as well as on different T-cell subsets. We show that B7-H3 does not costimulate human T cells. In the presence of strong activating signals, B7-H3 potently and consistently down-modulated human T-cell responses. This inhibitory effect was evident when analysing proliferation and cytokine production and affected naïve as well as pre-activated T cells. Furthermore, we demonstrate that B7-H3–T-cell interaction is characterised by an early suppression of IL-2 and that T-cell inhibition can be reverted by exogenous IL-2. Since the triggering receptor expressed on myeloid cells like transcript 2 (TREML2/TLT-2) has been recently described as costimulatory receptor of murine B7-H3 we have extensively analysed interaction of human B7-H3 with TREML2/TLT-2. In these experiments we found no evidence for such an interaction. Furthermore, our data do not point to a role for murine TREML2 as a receptor for murine B7-H3.
Item Type: | Journal Article | ||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | European Journal of Immunology | ||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
ISSN: | 0014-2980 | ||||
Official Date: | July 2009 | ||||
Dates: |
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Volume: | Vol.39 | ||||
Number: | No.7 | ||||
Page Range: | pp. 1754-1764 | ||||
DOI: | 10.1002/eji.200839028 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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