Year: 2020
Type: article
Abstract: Immunological synapse formation between cytotoxic T lymphocytes (CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosome to a position beneath the synaptic membrane. Centrosome polarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforin and granzymes toward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centriole deletion altered microtubule architecture as expected but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLs lacking centrioles did display substantially reduced killing potential, which was associated with defects in both lytic granule biogenesis and synaptic actin remodeling. These results reveal an unexpected role for the intact centrosome in controlling the capacity but not the specificity of cytotoxic killing.
Authors: Fella Tamzalit, Diana Tran, Weiyang Jin, Vitaly Boyko, Hisham Bazzi, Ariella Kepecs, Lance C. Kam, Kathryn V. Anderson, Morgan Huse
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G2051006376, G289723095, Immunology and Microbial Pathogenesis Research Training Program, Advanced Rigidity-based Material for Enhanced Immunotherapy, Dynamics of Primary Cilia Formation During Mammalian Development, G9000003249, Cancer Center Support Grant, Mechanoregulation of cytotoxic lymphocyte function
OpenAlex ID: W3005178835