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
✍ Scribed by Gina Lisignoli; Stefania Toneguzzi; Anna Piacentini; Sandra Cristino; Luca Cattini; Francesco Grassi; Andrea Facchini
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 530 KB
- Volume
- 198
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
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, TNFα and IFNγ, 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 IFNγ, either alone or in combination with TNFα, significantly up‐regulates the expression of CD54 and CD106 and induces the expression and release of CXCL9, CXCL10, CXCL11 in OB. The supernatant of TNFα‐ and IFNγ‐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 TNFα‐ and IFNγ‐activated OB or by incubation with the supernatant of TNFα‐ and IFNγ‐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. J. Cell. Physiol. 198: 388–398, 2004© 2003 Wiley‐Liss, Inc.