Leitner Judith, Klauser Christoph, Pickl Winfried F, Stöckl Johannes, Majdic Otto, Bardet Anaïs F, Kreil David P, Dong Chen, Yamazaki Tomohide, Zlabinger Gerhard, Pfistershammer Katharina, Steinberger Peter
Institute of Immunology, Center of Physiology, Pathophysiology and Immunology, Medical University Vienna, Austria.
Eur J Immunol. 2009 Jul;39(7):1754-64. doi: 10.1002/eji.200839028.
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.
B7-H3属于B7超家族，这是一组共刺激或下调T细胞反应的分子。虽然有研究表明B7-H3可抑制T细胞反应，但多项研究——其中大部分是在小鼠系统中进行的——发现B7-H3具有共刺激作用。在本研究中，我们通过评估该分子在不同实验条件下以及对不同T细胞亚群的作用，专门探讨了人B7-H3潜在的功能二元性。我们发现B7-H3不会共刺激人T细胞。在存在强激活信号的情况下，B7-H3能有效且持续地下调人T细胞反应。在分析增殖和细胞因子产生时，这种抑制作用很明显，且对初始T细胞以及预激活T细胞均有影响。此外，我们证明B7-H3与T细胞的相互作用以早期抑制白细胞介素-2为特征，并且外源性白细胞介素-2可逆转T细胞抑制。由于最近已将髓系细胞上表达的触发受体样转录本2（TREML2/TLT-2）描述为小鼠B7-H3的共刺激受体，我们广泛分析了人B7-H3与TREML2/TLT-2的相互作用。在这些实验中，我们没有发现这种相互作用的证据。此外，我们的数据也未表明小鼠TREML2作为小鼠B7-H3受体的作用。
