The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges

Abstract

Cytotoxic T lymphocytes (CTL) rapidly destroy their targets. Here we show that although target cell death occurs within 5 min of CTL-target cell contact, an immunological synapse similar to that seen in CD4 cells rapidly forms in CTL, with a ring of adhesion proteins surrounding an inner signaling molecule domain. Lytic granule secretion occurs in a separate domain within the adhesion ring, maintaining signaling protein organization during exocytosis. Live and fixed cell studies show target cell plasma membrane markers are transferred to the CTL as the cells separate. Electron microscopy reveals continuities forming membrane bridges between the CTL and target cell membranes, suggesting a possible mechanism for this transfer.

Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal

“…It is uncertain how often large amounts of IL-2 or IL-15 are readily available in vivo. IL-2 is vectorially secreted by CD4 + T helper cells [58,59], suggesting that exposure is normally carefully regulated. However, because IL-2 is a secreted protein, localized excesses are possible.…”

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…These nanotubes were shown to facilitate the transfer of lipid organelles between cells through actindependent mechanism. Nanotube structures were also reported to connect a wide range of immune cells, such as T cells, B cells, NK cells, and monocytes (24,75). In the event of disassembly of immunological synapse, formation of membrane nanotubes was observed between B cells and NK cells (76).…”

“…Of late new reports of intercellular membrane transfer started pouring in. It was demonstrated that T cells can acquire not only the MHC class I and class II proteins (18,19), but also the costimulatory proteins (20)(21)(22), the membrane fragments (23,24) from APCs and the proteins from endothelial cells (25). Till recently, the protein transfer by trogocytosis is believed to be unidirectional in murine system (1).…”

“…Here, T cells can acquire both MHC class I and class II proteins from APCs (19,23,24,(53)(54)(55). Reports of intercellular transfer of membrane fragments from APCs to T cells (24,54) and from target cells to NK cells (31), and even through homotypic interactions between cells like Daudi cells (56), are consistent with the membrane transfer mechanism that involves the transfer of membrane fragments derived from the intercellular contact or IS (57). One possible mechanism of intercellular transfer of membrane fragment might be that the MHC proteins and the other APC ligands are pulled during T-cell-receptor internalization (9), and the created force might break the high-avidity protein-protein interactions.…”

Une étape de maturation terminale des granules cytotoxiques est nécessaire à l’excrétion de leur contenu lytique

“…Ce mécanisme de maturation tardive pourrait également permettre de contrôler le nombre de granules cytotoxiques capables d'excréter leur contenu à la SI, et ainsi réguler précisément l'intensité d'une réponse cytotoxique. Il est également possible que ce même mécanisme de contrôle permette aux cellules cytotoxiques de disposer d'une fonction cytotoxique itérative leur conférant ce comportement de « tueur en série» qui les caractérise [2,10]. …”