The Direction of Plasma Membrane Exchange between Lymphocytes and Accessory Cells by Trogocytosis Is Influenced by the Nature of the Accessory Cell

Abstract

Exchange of plasma membrane fragments, including cell-surface proteins and lipids, in conjugates formed between lymphocytes and their cellular partners is a field of intense investigation. Apart from its natural occurrence during Ag recognition, the process of membrane transfer can be triggered in experimental or therapeutic settings when lymphocytes targeted by Abs are conjugated to FcγR-expressing accessory cells. The direction of membrane capture (i.e., which of the two cells is going to donate or accept plasma membrane fragments) can have important functional consequences, such as insensitivity of tumor cells to treatment by therapeutic mAbs. This effect, called antigenic modulation or shaving, occurs as a result of a process in which the FcγR-expressing cells remove the mAb and its target protein from the tumor cells. We therefore analyzed this process in conjugates formed between various FcγR-expressing cells and a series of normal or tumor T and B cells opsonized with different Abs capable of triggering membrane exchange (including the therapeutic Ab rituximab). Our results show that the direction of membrane capture is dictated by the identity of the FcγR-expressing cell, much more so than the type of lymphocyte or the Ab used. We found that monocytes and macrophages are prone to be involved in bidirectional trogocytosis with opsonized target cells, a process they can perform in parallel to phagocytosis. Our observations open new perspectives to understand the mechanisms involved in trogocytosis and may contribute to optimization of Ab-based immunotherapeutic approaches.

Plasma‐dependent, antibody‐ and Fcγ receptor‐mediated translocation of CD8 molecules from T cells to monocytes

“…6B). These phenomena are consistent with the Ag/Ab immune complexes and FccRmediated trogocytosis (6). The first important issue in this study is that plasma was found to be essential for the completion of this type of trogocytosis.…”

“…Furthermore, it was confirmed that after coculturing monocytes with fluorescence-conjugated anti-CD8-labeled T cells, the fluorescent signal was evident on the monocytes. These phenomena are consistent with Ab-dependent and FccR-mediated trogocytosis, which is recently recognized as one of the intercellular communication processes of the immune system (6). Trogocytosis means exchange of plasma membrane, cell surface molecules and all, in conjugates formed between immune cells.…”

“…These cells can accept the plasma membrane fragments from partner cells after recognition of cell surface Ag on the partner cells by a specific receptor on the cell surface. Recently, another mechanism of trogocytosis mediated by Ag/Ab immune complexes and FccRs on acceptor cells was identified (6). This mechanism is well characterized as the phenomenon wherein CD20 molecules on malignant B cells are lost after infusion of the humanized anti-CD20 mAb, rituximab (23,24).…”

CD20+T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer

“…13 During trogocytosis, intact proteins, protein complexes and/or even membrane patches are transferred from one cell type to the other. [14][15][16][17] In addition to HLA-DR transfer, other accessory molecules involved in this contact were found to be similarly transferred. 18 Interestingly, we and others have recently demonstrated the presence of a small population of T-cells that express the B-cell marker CD20 in the peripheral blood of healthy volunteers and patients suffering from rheumatoid arthritis.…”

CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity

“…29 The direction of plasma membrane exchange between lymphocytes and accessory cells by trogocytosis is influenced by the nature of accessory cells. 30 Another potential mechanism for trogocytosis is via exosome fusion to acceptor cells or internalization and recycling of exosomal molecules on the acceptor cells. 31 The exosomal molecules on acceptor cells are quite stable and can last as long as 12 days in culture.…”