Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells

Abstract

Trogocytosis is the uptake of membrane fragments from one cell by another and has been described for immune cells in mice and humans. Functional consequences of trogocytosis are emerging, but a dramatic immune function has still to be associated with it. Here we show that some resting, and most activated, CD4⁺ and CD8⁺ T cells acquire immunosuppressive HLA-G1 from antigen-presenting cells (APCs) in a few minutes. Acquisition of HLA-G through membrane transfers does not change the real nature of the T cells but immediately reverses their function from effectors to regulatory cells. These regulatory cells can inhibit allo-proliferative responses through HLA-G1 that they acquired. These data demonstrate that trogocytosis of HLA-G1 leads to instant generation of a new type of regulatory cells, which act through cell-surface molecules they temporarily display but do not express themselves. Such regulatory cells whose existence is most likely limited in space and time might constitute an “emergency” immune suppression mechanism used by HLA-G–expressing tissues to protect themselves against immune aggression. In addition, T cells acquire from HLA-G–expressing APCs their HLA-G–dependent capability to induce the slower differentiation of regulatory cells that act independently of HLA-G. These data re-emphasize the significance of HLA-G expression in normal and pathologic situations.