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

Eur J Immunol. 1995 Jul;25(7):2027-33. doi: 10.1002/eji.1830250734.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific
  • CD28 Antigens / physiology*
  • CD3 Complex / physiology*
  • Calcium / metabolism
  • Cell Adhesion Molecules / physiology*
  • Cytotoxicity, Immunologic*
  • Humans
  • Immunity, Cellular
  • In Vitro Techniques
  • Ki-1 Antigen / metabolism
  • Lymphocyte Subsets / immunology*
  • Major Histocompatibility Complex
  • Phosphoproteins / metabolism
  • Phosphorylation
  • T-Lymphocytes, Cytotoxic / immunology*


  • Antibodies, Bispecific
  • CD28 Antigens
  • CD3 Complex
  • Cell Adhesion Molecules
  • Ki-1 Antigen
  • Phosphoproteins
  • Calcium