Abstract
Cytotoxic immunity relies on specialized effector T cells, the cytotoxic T cells, which are endowed with specialized cytolytic machinery that permits them to induce death of their targets. Upon recognition of a target cell, cytotoxic T cells form a lytic immune synapse and by docking the microtubule-organizing center at the synaptic membrane get prepared to deliver a lethal hit of enzymes contained in lytic granules. New insights suggest that the directionality of lytic granule trafficking along the microtubules represents a fine means to tune the functional outcome of the encounter between a T cell and its target. Thus, mechanisms regulating the directionality of granule transport may have a major impact in settings characterized by evasion from the cytotoxic response, such as chronic infection and cancer. Here, we review our current knowledge on the signaling pathways implicated in the polarized trafficking at the immune synapse of cytotoxic T cells, complementing it with information on the regulation of this process in natural killer cells. Furthermore, we highlight some of the parameters which we consider critical in studying the polarized trafficking of lytic granules, including the use of freshly isolated cytotoxic T cells, and discuss some of the major open questions.
Highlights
Specialty section: This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology
We highlight some of the parameters which we consider critical in studying the polarized trafficking of lytic granules, including the use of freshly isolated cytotoxic T cells, and discuss some of the major open questions
We still lack information about the T cell receptors (TCRs) signaling originating at the central supramolecular activation cluster (cSMAC) that determines the directionality of granule trafficking, rapid Ca2+ kinetics and the activation of linker for activation of T cells (LAT) may serve as indicators of the successful granule polarization at the Cytotoxic T lymphocytes (CTLs) synapse
Summary
Reviewed by: Andres Alcover, Institut Pasteur, France Christoph Wülfing, University of Bristol, United Kingdom. Upon recognition of a target cell, cytotoxic T cells form a lytic immune synapse and by docking the microtubule-organizing center at the synaptic membrane get prepared to deliver a lethal hit of enzymes contained in lytic granules. CTLs bear T cell receptors (TCRs) through which they bind antigenic peptides presented on the major histocompatibility complex (MHC) molecules of target cells. In this way, they successfully discriminate between healthy cells and those presenting non-self peptides, typically of neoplastic or microbial origin. As consequence of non-self recognition, CTLs attack and lyse malignant and infected cells In this context, an impaired functioning of CTLs may lead to immune evasion of tumors and the insurgence of chronic infections. Exocytosis of secretory lysosomes at the synapse leads to a focal release of lytic enzymes into the synaptic cleft and promotes the surface exposure of FasL, implementing two major mechanisms of intrinsic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
