B7‐H3 is a potent inhibitor of human T‐cell activation: No evidence for B7‐H3 and TREML2 interaction
Open Access
- 6 July 2009
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 39 (7), 1754-1764
- https://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.Keywords
This publication has 36 references indexed in Scilit:
- The capacity of the TNF family members 4‐1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cellsEuropean Journal of Immunology, 2008
- The tumor microenvironment and its role in promoting tumor growthOncogene, 2008
- Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responsesProceedings of the National Academy of Sciences of the United States of America, 2008
- B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcomeProceedings of the National Academy of Sciences of the United States of America, 2007
- Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell ResponsesImmunity, 2007
- Direct stimulation of T lymphocytes by immunosomes: Virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory moleculesProceedings of the National Academy of Sciences of the United States of America, 2006
- No evidence for dualism in function and receptors: PD‐L2/B7‐DC is an inhibitory regulator of human T cell activationEuropean Journal of Immunology, 2006
- MUSCLE: multiple sequence alignment with high accuracy and high throughputNucleic Acids Research, 2004
- A general method applicable to the search for similarities in the amino acid sequence of two proteinsJournal of Molecular Biology, 1970