ICAM‐3, the third LFA‐1 counterreceptor, is a co‐stimulatory molecule for both resting and activated T lymphocytes

摘要

AbstractOptimal activation of human T cells mediated by ligation of CD3/T cell receptor (TcR) complex requires co‐stimulatory signals. These can be provided by the adhesive interaction between receptor molecules on T cells and their counter‐receptors on antigen‐presenting cells. Soluble ICAM‐3, anti‐ICAM‐3 and anti‐CD3 mAb were utilized to address the role of the ICAM‐3/LFA‐1 pathway in TcR/CD3‐dependent or ‐independent T cell activation. Immunoaffinity‐purified ICAM‐3 co‐immobilized with suboptimal concentrations of anti‐CD3 monoclonal antibody (mAb) stimulated T lymphocytes as monitored by the expression of the lymphocyte activation antigens CD25 and CD69. The mechanism underlaying this activation appear to involve the interaction of ICAM‐3 with a β2 integrin, likely to be LFA‐1, since mAb to the CD18 chain completely inhibited T cell activation. Similar experiments demonstrated that anti‐ICAM‐3 mAb were able to co‐stimulate both resting (cord blood) and activated (T cell clones) T lymphocytes. On the contrary, anti‐ICAM‐1 mAb were only co‐stimulatory for CD25 expression on activated but not on resting T cells. In addition, we have found that some γδ T cell clones bearing the Vδ1 segment were activated by direct mAb engagement of ICAM‐3 in the absence of TcR/CD3 occupancy. Furthermore, immobilized anti‐ICAM‐3 mAb also induced development of dentritic processes. In conclusion, our data suggest that ICAM‐3 on the surface of both T cells and antigen‐presenting cells plays