Role of naive and memory T cells in tumor cell lysis mediated by bi-specific antibodies

Immunobiology. 1997 Jun;197(1):122-32. doi: 10.1016/S0171-2985(97)80062-9.

Abstract

Bispecific monoclonal antibodies (Bi-mAb) with specificity for a tumor associated antigen and the CD3 or CD28 antigen on T lymphocytes, respectively, induce activation of resting T lymphocytes and target-specific tumor cell lysis. Former studies had confirmed that T cells expressing the CD45RO "memory" antigen at high levels were the most potent effectors of Bi-mAb-mediated cytotoxicity when compared to their "naive" counterparts expressing the CD45RA antigen. Further analysis of the T cell subpopulations revealed that within the memory T cell pool, CD8+ T cells were the effector cell, population with strongest cytolytic activity. The cytolytic activity was correlated with the expression level of perforin and granzymes B mRNA. Ca2+ complexing agents, which abrogate perforin activity, reduced necrosis, while inhibition of granzyme activity in effector or target-cells had a similar effect on apoptosis. These results confirm the crucial role perforin and granzymes play in target-cell lysis and explain why CD8+CD45RO+ T cells activated by combined CD3 and CD28 antigen triggering represent the T cell pool with highest cytolytic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bispecific / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Biomarkers, Tumor / immunology*
  • CD28 Antigens / immunology
  • CD3 Complex / immunology
  • Cytotoxicity, Immunologic*
  • Humans
  • Immunologic Memory*
  • Interphase / immunology*
  • Ki-1 Antigen / immunology
  • Lymphocyte Activation
  • Lymphocyte Subsets / enzymology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / genetics
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Serine Proteinase Inhibitors / pharmacology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Up-Regulation / immunology

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • CD28 Antigens
  • CD3 Complex
  • Ki-1 Antigen
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Serine Proteinase Inhibitors
  • Perforin