Cell death mechanisms induced by cytotoxic lymphocytes

Cell Mol Immunol. 2009 Feb;6(1):15-25. doi: 10.1038/cmi.2009.3.


One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+ T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Apoptosis / immunology*
  • Cytotoxicity, Immunologic*
  • Exocytosis / immunology
  • Fas Ligand Protein / metabolism
  • Fas-Associated Death Domain Protein / metabolism
  • Granzymes / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Models, Biological*
  • Perforin / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, Differentiation, T-Lymphocyte
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • GNLY protein, human
  • Tumor Necrosis Factor-alpha
  • Perforin
  • Granzymes