Abstract A070: The role of the centrosome in cytotoxic T cell function

摘要: Cytotoxic T lymphocytes (CTLs) are essential for productive immune responses and recent studies have demonstrated their strong clinical potential as immunotherapeutic agents against established tumors. in CTLs induced by the cell receptor, which recognizes cognate peptide-major histocompatibility complex molecules on surfaces of infected or transformed cells, induces formation immunological synapse. Synapse is accompanied a series actin microtubule remodeling events, most striking dramatic reorientation centrosome to position just beneath center contact site. It has been proposed that lytic granules containing perforin granzyme cluster around activated CTLs. This polarization toward synapse promotes selective fusion these with synaptic membrane, leading directional release contents target cell. In order study more precisely how influences secretory contributions affect CTL activity, we developed an approach using OT-I mice bearing conditional allele both p53 (p53flox) well SAS4 (SAS4flox), scaffolding protein absolutely required maintenance centrosome. SAS4−/−p53−/− cells were generated transducing SAS4flox/floxp53flox/flox retrovirus expressing Cre. Using gamma-tubulin pericentrin staining, able show deletion effectively eliminates interphase centrosomes SAS4−/− p53−/− exhibited marked defect killing after 24h, implying crucial role cytotoxic responses. was decrease B production. IFN-gamma production secretion not altered loss Importantly, TCR signaling normal cells. summary, impairs without altering overall magnitude. Given importance delivery, can assume ablation selectively alters efficiency disrupting secretion. Citation Format: Fella Tamzalit, Ariella Kepecs, Hisham Bazzi, Kathryn Anderson, Morgan Huse. The function [abstract]. In: Proceedings Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Immunol Res 2016;4(11 Suppl):Abstract nr A070.