Icam - melanoma cells are relatively resistant to cd3-mediated t-cell lysis

✍ Scribed by Eric Braakman; Peter S. Goedegebuure; Rea J. Vreugdenhil; David M. Segal; Stephen Shaw; Reinder L. H. Bolhuis

• Book ID: 102866389
• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: French
• Weight: 794 KB
• Volume: 46
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910460325

✦ Synopsis

The primary activation pathway of T cells is via the T-cell receptor (TCR)/CD3 complex, which is functionally interrelated with various accessory molecules. We examined the contribution of the lymphocyte-function-associated antigen-IIintercellular adhesion molecule I (LFA-IIICAM-I) interaction to CD3mCR-mediated lysis by cytotoxic T lymphocytes (CTL). We used ICAM-IPor+ tumor cell lines as target cells and anti-CD3-or anti-LFA-I containing hetero-cross-linked monoclonal antibody (MAb) to bridge CTL and target cells and simultaneously to activate CTL. The ICAM-I-melanoma-derived cell line lgR39 was relatively resistant to CD3mediated lysis by both TCRaP+ and TCRyG+ CTL, when compared with ICAM-I+ cell lines. Induction of ICAM-I on the membrane of lgR39 cells by tumor necrosis factor (TNF) rendered these cells more susceptible to CD3-mediated lysis. Anti-ICAM-I MAb inhibited this TNF-enhanced susceptibility to lysis, directly demonstrating that the induction of ICAM-I was critical in the TNF-induced increase in susceptibility to lysis of IgR39 cells. CTL formed less efficient conjugates with the ICAM-I -cells as compared to ICAM-I + cells. Both spontaneous and CD3-induced conjugate formation as well as CD3-mediated lysis of ICAM-I-tumor cells by CTL were enhanced by the addition of anti-LFA-I containing heterocross-linked MAb, thereby mimicking the LFA-IIICAM-I interaction between CTL and target cells. Soluble anti-CD I8 MAb inhibited CD3-mediated lysis of ICAM-I-target cells by CTL without affecting their conjugate formation. Anti-LFA-I MAb added after conjugate formation still inhibited lysis of both ICAM-I +Or-tumor cells. Taken together, these findings suggest that the LFA-IIICAM-I interaction co-activates CD3I TCR-mediated lysis by CTL through both an enhanced CTLtarget cell binding and the delivery of post-conjugate costimulatory signals.