Recruitment and proliferation of T lymphocytes is supported by IFNγ- and TNFα-activated human osteoblasts:: Involvement of CD54 (ICAM-1) and CD106 (VCAM-1) adhesion molecules and CXCR3 chemokine receptor
Recruitment and proliferation of T lymphocytes is supported by IFNγ- and TNFα-activated human osteoblasts:: Involvement of CD54 (ICAM-1) and CD106 (VCAM-1) adhesion molecules and CXCR3 chemokine receptor
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DOI：
10.1002/jcp.10427
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发表时间：
2004-03-01
影响因子：
5.6
通讯作者：
Facchini, A
中科院分区：
文献类型：
--
作者：
Lisignoli, G;Toneguzzi, S;Facchini, A
成骨细胞（OB）在炎症过程中相互作用并调节T淋巴细胞表型和增殖的机制尚不清楚。通过实时PCR、流式细胞术和免疫组织化学在人OB原代培养物中评估两种调节性细胞因子TNF α和IFN γ对CD 54（ICAM-1）和CD 106（VCAM-1）粘附分子以及CXCR 3配体（CXCL 9、CXCL 10、CXCL 11）表达的影响。此外，我们功能性地评估了与静止或刺激的OB一起生长的T淋巴细胞的募集和增殖。根据目前的数据，IFN γ单独或与TNF α组合显著上调OB中CD 54和CD 106的表达，并诱导CXCL 9、CXCL 10、CXC 11的表达和释放。TNF α和IFN γ激活的OB的上清液比CXCR 3配体的刺激更显著地诱导T淋巴细胞的募集。通过与TNF α和IFN γ激活的OB直接接触或通过与TNF α和IFN γ激活的OB的上清液孵育，T淋巴细胞增殖显著增强。用抗CD 11 a、抗CD 49 d、抗CXCR 3和百日咳杆菌毒素进行的阻断实验证明粘附分子和CXCR 3趋化因子受体在T淋巴细胞增殖中起关键作用。本研究表明，参与的粘附分子（CD 11 a和CD 49 d）和趋化因子受体（CXCR 3）的机制，OB招募，相互作用，并调节T淋巴细胞增殖炎症条件下。(C)2003 Wiley-Liss，Inc.
The mechanism by which osteoblasts (OB) interact and modulate the phenotype and proliferation of T lymphocytes during inflammation is not well known. The effects of two regulatory cytokines, TNFalpha and IFNgamma, on the expression of CD54 (ICAM-1) and CD106 (VCAM-1) adhesion molecules and the CXCR3 ligands (CXCL9, CXCL10, CXCL11), were assessed in a primary culture of human OB by real-time PCR, flow cytometry, and immunohistochemistry. in addition, we functionally evaluated the recruitment and proliferation of T lymphocytes grown with resting or stimulated OB. According to the present data IFNgamma, either alone or in combination with TNFa, significantly up-regulates the expression of CD54 and CD106 and induces the expression and release of CXCL9, CXCL10, CXC11 in OB. The supernatant of TNFalpha- and IFNgamma-activated OB induces the recruitment of T lymphocytes more significantly than stimulation by CXCR3 ligands. T lymphocyte proliferation is significantly enhanced by direct contact with TNFa- and IFNgamma-activated OB or by incubation with the supernatant of TNFalpha- and IFNgamma-activated OB. Blocking experiments with anti-CD11a, anti-CD49d, anti-CXCR3, and Bordetella pertussis toxin demonstrate that adhesion molecules and the CXCR3 chemokine receptor play a key role in the proliferation of T lymphocytes. The present study demonstrates the involvement of adhesion molecules (CD11a and CD49d) and chemokine receptor (CXCR3) in the mechanism by which OB recruit, interact, and modulate T lymphocyte proliferation under inflammatory conditions. (C) 2003 Wiley-Liss, Inc.