Cytotoxic T cells are immune cells important in the destruction of pathogen-infected and tumor cells. This function is dependent on specific recognition of the target cell, through the T cell receptor, and the subsequent secretion of specific lysosomes called lytic granules. One cytotoxic T cell can kill multiple target cells during a given immune response. Therefore, the secretion of lytic granules must be well regulated to ensure that the T cells affect the correct targets.
The cytosol of animal cells is enclosed by a network of cortical actin that touches the cell plasma membrane. Decreases in the density of cortical actin influences the granule secretion of various cell types. Changes in cortical actin occur at the time that cytotoxic T cells responds to a target. A decrease in the density of cortical actin in the area between the T cell and its target leads to lytic granule secretion. It is not fully understood how exactly changes in cortical actin levels regulate granule secretion to limit the cytotoxic effect to the target cell.
For a better understanding of the regulation of lytic granule secretion by cortical actin, researchers used special live-cell and internal reflection fluorescence microscopy techniques to study the activity of cortical actin prior to and throughout the process of lytic granule secretion. Transgenic mouse cytotoxic T cells that recognize an ovalbumin peptide were used to study cortical actin changes during cytotoxic T cell activity. At the synapse between the T cells and its target (ovalbumin-containing EL4 mouse lymphoma cells), there was a decrease in cortical actin density after the T cells became in contact with the target. Then, secretion of lytic granules occurred as evidenced by Ca2+ flux in the target cells. After the Ca2+ flux, cortical actin density returned to its original ‘resting’ state. This suggests that cortical actin recovers in cytotoxic T cells after lytic granule secretion, and effectively dampens further secretion.
For a closer look, cytotoxic T cells were transfected with fluorescent markers for lytic granules. Activation of the T cells led to a rapid decrease in cortical actin density at the synapse and movement of lytic granules as observed in real time using total internal reflection fluorescence microscopy. The data provided by this study suggest that cortical actin recovery regulates cytotoxic T cell lytic granule secretion, which promotes the T cells’ ability to kill multiple cells during a single immune response.
Ritter AT, e. (2017). Cortical actin recovery at the immunological synapse leads to termination of lytic granule secretion in cytotoxic T lymphocytes. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 2 August 2017, from https://www.ncbi.nlm.nih.gov/pubmed/28716933