The role of lymphocyte subsets and adhesion molecules in T cell‐dependent cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies
- 1 July 1995
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 25 (7), 2027-2033
- https://doi.org/10.1002/eji.1830250734
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 Ca2+. 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.Keywords
This publication has 30 references indexed in Scilit:
- T cell receptor stimulation, but not CD28 costimulation, is dependent on LFA‐1‐mediated eventsEuropean Journal of Immunology, 1994
- Endothelial Cells Promote Anti‐CD3‐Induced T‐cell Proliferation via Cell‐Cell Contact Mediated by LFA‐1 and CD2Scandinavian Journal of Immunology, 1993
- CD30‐antigen‐specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: Potential use for the treatment of hodgkin's lymphomaInternational Journal of Cancer, 1993
- Hodgkin's cells express a novel pattern of adhesion moleculesClinical and Experimental Immunology, 1992
- CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes.The Journal of Experimental Medicine, 1992
- Production of tumor necrosis factor-α by naive or memory T lymphocytes activated via CD28Cellular Immunology, 1992
- Remote T cell co‐stimulation via LFA‐1/ICAM‐1 and CD2/LFA‐3: Demonstration with immobilized ligand/mAb and implication in monocyte‐mediated co‐stimulationEuropean Journal of Immunology, 1991
- Role of Lymphocyte Adhesion Receptors in Transient Interactions and Cell LocomotionAnnual Review of Immunology, 1991
- Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsetsImmunology Today, 1988
- Requirements for activation of human peripheral blood T cells by mouse monoclonal antibodies to CD3Clinical Immunology and Immunopathology, 1987