Role ofβ2 Integrins in the Binding of Thymocytes to RatThymic Macrophages

摘要

A role of β2 integrins and one of their ligands, ICAM-1, in thymic macrophage(TMF)/thymocyte interactions was studied. TMF were isolated as adherent cells from 4-dayold culture of thymic-cell suspensions either from normal or hydrocortisone-treated rats.Adherent cells were 94-98% positive with ED1 (a pan-macrophage marker). The majorityof them (75-95%) expressed the CD11b and CD18 molecules, and 60-70% expressed CD54(ICAM-1). A low proportion of TMF (10-20%) expressed CDlla (LFA-1). The expressionof all these antigens was upregulated by IFN-α and TNF-α. The effect of these mAbs onTMF/thymocyte binding was studied using a simple rosette assay by incubating unstimulatedor IFN-γ or TNF-α stimulated TMF, grown on microscopic slides with resting orConA +IL-2 activated thymocytes. It was found that LFA-1/CD18 and ICAM-1 play asignificant role in the TMF/thymocyte adhesion. In addition, a LFA-l-dependent/ICAM-1-independent adhesion pathway was observed, suggesting that LFA-1 might use anotherligand. The inhibitory effect of anti-CD18 mAb (WT-3) was higher than the effect ofanti-LFA-1 mAb (WT-1) and was a consequence of blocking the CD18 chain both onthymocytes and TMF. No significant difference in the expression and function of adhesionmolecules was found between TMF obtained from normal or hydrocortisone-treated rats.The involvement of CD1 1b in these processes was of lesser importance than the role of theCD11a molecule. By using mAbs to different epitopes of the CD11b molecule, such asOX-42 (anti-CD11b/CD11c), ED7, and ED8 (anti-CD11b), it was found that they wereeither slightly or moderately inhibitory under certain experimental conditions or did notsignificantly modulate TMF/thymocyte binding. Oχ-42 was slightly stimulatory in someexperiments. Cumulatively, these results show that 2 integrins play a significant role inTMF/thymocyte interactions and probably contribute to T-cell development in vivo.