Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one ac...Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one acceptor cell type. Here, we studied trogocytosis in a more complex system, involving not only several immune cell subsets but also multiple tumor cells. We show that CD4~ T cells, CD8＋ T cells and monocytes can acquire membrane patches and the intact proteins they contain from different tumor cells by multiple simultaneous trogocytoses. The trogocytic ca- pabilities of CD4~ and CD8~ T cells were found to be similar, but inferior to that of autologous monocytes. Activated peripheral-blood mononuclear cells （PBMCs） may also exchange membranes between themselves in an all-autolo- gous system. For this reason, monocytes are capable of acquiring membranes from multiple tumor cell sources, and transfer them again to autologous T cells, along with some of their own membranes （serial trogocytosis）. Our data illustrate the extent of membrane exchanges between autologous activated immune effector cells and their environ- ment, and how the cellular content of the local environment, including ＂bystander＂ cells, may impact the functions of immune effector cells.展开更多
Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-...Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-presenting cells and their functions can be modulated following trogocytosis. However, it is not known whether induced regulatory T cells （iTregs） can undergo trogocytosis, and if so, what the functional consequences of this process might entail. In this study, we show that iTregs can be generated from CD80-/-CD86-/- double knockout （DKO） mice. Using flow cytometry and confocal fluorescence microscopy, we demonstrate that iTregs generated from DKO mice are able to acquire both CD80 and CD86 from mature dendritic cells （mDCs） and that the acquisition of CD86 occurs to a higher extent than that of CD80. Furthermore, we found that after co-incubation with iTregs, dendritic cells （DCs） downregulate their surface expression of CD80 and CD86. The trogocytosis of both CD80 and CD86 occurs in a cytotoxic T lymphocyte-associated antigen-4 （CTLA-4）, CD28 and programmed death ligand-1 （PDL1）-independent manner. Importantly, we showed that iTregs that acquired CD86 from mDCs expressed higher activation markers and their ability to suppress naive CD4＋ T-cell proliferation was enhanced, compared to iTregs that did not acquire CD86. These data demonstrate, for the first time, that iTregs can acquire CD80 and CD86 from mDCs, and the acquisition of CD86 may enhance their suppressive function. These findings provide novel understanding of the interaction between iTregs and DCs, suggesting that trogocytosis may play a significant role in iTreg-mediated immune suppression.展开更多
The classical view of signaling between cells of immune system includes two major routes of intercellular communication:Through the release of extracellular molecules or a direct interaction between membrane bound rec...The classical view of signaling between cells of immune system includes two major routes of intercellular communication:Through the release of extracellular molecules or a direct interaction between membrane bound receptor and its membrane bound ligand,which initiate a cascade of signaling in target cell.However,recent studies indicate that besides these canonical modes of signaling there are also noncanonical routs of intercellular communications through membrane stripping/membrane exchange/trogocytosis,extracellular traps,exosomes and ectososmes/microparticles.In this review we discuss what are the components of noncanonical pathways of signaling and what role they play in immune cells interactions.展开更多
文摘Trogocytosis is a rapid transfer between cells of membranes and associated proteins. Trogocytic exchanges have been investigated between different cell types, mainly in two-cell systems, involving one donor and one acceptor cell type. Here, we studied trogocytosis in a more complex system, involving not only several immune cell subsets but also multiple tumor cells. We show that CD4~ T cells, CD8＋ T cells and monocytes can acquire membrane patches and the intact proteins they contain from different tumor cells by multiple simultaneous trogocytoses. The trogocytic ca- pabilities of CD4~ and CD8~ T cells were found to be similar, but inferior to that of autologous monocytes. Activated peripheral-blood mononuclear cells （PBMCs） may also exchange membranes between themselves in an all-autolo- gous system. For this reason, monocytes are capable of acquiring membranes from multiple tumor cell sources, and transfer them again to autologous T cells, along with some of their own membranes （serial trogocytosis）. Our data illustrate the extent of membrane exchanges between autologous activated immune effector cells and their environ- ment, and how the cellular content of the local environment, including ＂bystander＂ cells, may impact the functions of immune effector cells.
文摘Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-presenting cells and their functions can be modulated following trogocytosis. However, it is not known whether induced regulatory T cells （iTregs） can undergo trogocytosis, and if so, what the functional consequences of this process might entail. In this study, we show that iTregs can be generated from CD80-/-CD86-/- double knockout （DKO） mice. Using flow cytometry and confocal fluorescence microscopy, we demonstrate that iTregs generated from DKO mice are able to acquire both CD80 and CD86 from mature dendritic cells （mDCs） and that the acquisition of CD86 occurs to a higher extent than that of CD80. Furthermore, we found that after co-incubation with iTregs, dendritic cells （DCs） downregulate their surface expression of CD80 and CD86. The trogocytosis of both CD80 and CD86 occurs in a cytotoxic T lymphocyte-associated antigen-4 （CTLA-4）, CD28 and programmed death ligand-1 （PDL1）-independent manner. Importantly, we showed that iTregs that acquired CD86 from mDCs expressed higher activation markers and their ability to suppress naive CD4＋ T-cell proliferation was enhanced, compared to iTregs that did not acquire CD86. These data demonstrate, for the first time, that iTregs can acquire CD80 and CD86 from mDCs, and the acquisition of CD86 may enhance their suppressive function. These findings provide novel understanding of the interaction between iTregs and DCs, suggesting that trogocytosis may play a significant role in iTreg-mediated immune suppression.
基金Supported by William Stamps Farish FundDonald D.Hammill Foundation
文摘The classical view of signaling between cells of immune system includes two major routes of intercellular communication:Through the release of extracellular molecules or a direct interaction between membrane bound receptor and its membrane bound ligand,which initiate a cascade of signaling in target cell.However,recent studies indicate that besides these canonical modes of signaling there are also noncanonical routs of intercellular communications through membrane stripping/membrane exchange/trogocytosis,extracellular traps,exosomes and ectososmes/microparticles.In this review we discuss what are the components of noncanonical pathways of signaling and what role they play in immune cells interactions.
