Natural Killer cells, as their name suggests, are the prime example of cytotoxic cells. However, NK cells aren’t your only option for cytotoxicity. Activated CD8+ T cells are the classic example of cytotoxic T cells, but CD4+ T cells have also been demonstrated to kill their targets. In this post, we’ll dive into the different types and functions of cytotoxic cells.

Cytotoxicity: How It Works

All cytotoxic cells kill their targets by releasing granzymes and perforin from intracellular granules to trigger programmed cell death (apoptosis) in cancerous cells or those infected with bacteria or a virus.

Researchers have traditionally used a chromium-51 assay to measure cell-mediated cytotoxicity, where target cells are labeled with radioisotope chromium-51. When the target cell dies, it releases the chromium into the supernatant for the researcher to measure. Newer methods that do not involve radioactivity have been developed, including bioluminescence-based cytotoxicity assays to measure the release of lytic molecules, such as granzymes or perforin, from the target cells.

Comparing NK Cells & Cytotoxic T Cells

When it comes to selecting the right cytotoxic cell for your experiments, which one do you choose? We compare and contrast the functionality and use cases of each below.

Natural Killer Cells


  • NK cells have cytotoxic granules already formed and are ready to kill target cells.
  • NK cells kill cells that have antibody bound to the surface. Examples include breast cancer cells with anti-HER2 antibody and leukemia cells with Campath bound to the surface. NK activity can be an important mechanism for antibody-based therapeutics.
  • NK cells target cells that have lost expression of MHC molecules, such as tumor cells or virus-infected cells.
  • Genetic matching between the NK cell and the target cell is not required.

Use Cases:

  • NK cells can be used to determine if an antibody-based therapeutic is effective at mediating cell death.
  • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): When an antibody binds to a protein on a target cell, the NK cell binds to the Fc receptor on the antibody. This binding triggers the NK cell to kill the target cell.
  • If you’re working on an antibody-based therapeutic, NK cells will be useful for testing ADCC for your antibody.


Cytotoxic T Cells


  • CD8+ T cells don’t have cytotoxic granules until they have been activated by their cognate antigen.
  • Antigen-specific T cells will only target cells that match the HLA allele and the antigen they recognize (e.g., HLA-A*0201 restricted CMV-specific T cells will only kill cells that express HLA-A*0201 and are CMV infected).
  • Genetic matching between the cytotoxic T cell and the target cell is required.

Use Cases:

  • CD8+ T cells can be used with bispecific antibodies to direct their cytotoxicity to the desired target cells.
  • CD8+ T cells are a good starting material for developing antigen-specific T cells.
  • Antigen-specific cytotoxic T cells (CTL) can be used as tools for detecting antigens presented by infected cells or tumor cells.
  • CTL can also serve as a model for engineering more efficient cytotoxicity.

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