The role of lymphocyte subsets and adhesion molecules in T cell-dependent cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies

✍ Scribed by Christoph Renner; Wolfram Jung; Ugur Sahin; Rene van Lier; Michael Pfreundschuh

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 776 KB
• Volume: 25
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830250734

✦ Synopsis

Abstract

The cure of human Hodgkin's tumors heterotransplanted into SCID mice can be achieved by two bispecific monoclonal antibodies (Bi‐mAb) directed against the tumor‐associated CD30 antigen and CD3 and CD28, respectively, and normal peripheral human blood T cells. We investigated the role of lymphocyte subsets and adhesion molecules in this Bi‐mAb‐mediated cytolysis. CD4^+^ lymphocytes were the most rapidly expanding subpopulation, but Bi‐mAb‐directed cytotoxicity was mediated preferentially by CD8^+^ lymphocytes and effector cells belonging to the CD45RO^+^ “memory” pool. Blocking of the LFA‐1/ICAM‐1 or CD2/LFA‐3 adhesion pathways by mAb decreased Bi‐mAb‐mediated cytotoxicity. This was not due to inhibition of aggregate formation between Bi‐mAb‐coated T lymphocytes and target cells. Cross‐linking of LFA‐1 or CD2 molecules on lymphocytes prestimulated with Bi‐mAb bound to CD3 and CD28 antigen lead to a more pronounced and prolonged rise in the intracellular concentration of free Ca^2+^. Additional CD2 cross‐linking resulted in the tyrosine phosphorylation of distinct proteins. These findings indicate that adhesion molecules play a critical role and function as co‐stimulatory signals rather than as cellular contact mediators in CD3 and CD28 Bi‐mAb‐stimulated T lymphocytes.