Cytolytic effector mechanisms of human CD4+ cytotoxic T lymphocytes

Hum Immunol. 1996 Jan;45(1):64-75. doi: 10.1016/0198-8859(95)00151-4.


To elucidate mechanisms by which human CD4+ cells mediated cytolytic activity, we studied the expression of cytolytic proteins and the effects of inhibitors and mAbs on T-cell clones. Of seven cytolytic CD4+ clones, three were specific for the HLA-DR17, while four recognized DR18. Anti-HLA-DR mAb and anti-CD4 mAb blocked lysis. In addition, N alpha-p-tosyl-L-lysine chloromethylketone (TLCK), a serine esterase inhibitor, as well as cytochalasin B and monensin, antagonists of secretory pathways, inhibited CD4+ CTLs, whereas the absence of extracellular Ca+2 or the presence of Ca+2 channel blockers partially inhibited cytotoxicity. CD4+ CTLs induced apoptosis of target cell nuclei and membrane damage simultaneously. The CD4+ clones synthesized perforin and granzyme B and expressed the granule-associated protein TIA-1. Our studies indicate that two distinct mechanisms may contribute to cytolysis by CD4+ clones: (1) a Ca+2-dependent mechanism associated with the cytotoxic granules and (2) a Ca+2-insensitive mechanism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • CD4-Positive T-Lymphocytes / classification*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology*
  • Calcium / physiology
  • Cell Nucleus / immunology
  • Clone Cells
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic* / drug effects
  • Exocytosis / immunology
  • Extracellular Space / immunology
  • Humans
  • Molecular Sequence Data
  • Protein Synthesis Inhibitors / pharmacology
  • T-Lymphocytes, Cytotoxic / immunology


  • Protein Synthesis Inhibitors
  • Calcium