Transfer of cell membrane components via trogocytosis occurs in CD4⁺Foxp3⁺CD25⁺ regulatory T-cell contact-dependent suppression

Abstract

A key component of the immune system is its ability to establish and maintain peripheral tolerance. Naturally occurring CD4⁺CD25⁺Foxp3⁺ regulatory T (nTreg) cells represent an important means by which this is accomplished, through their potent ability to suppress the actions of both CD4⁺ and CD8⁺ effector (Teff) cells in vitro and in vivo. We hypothesized that direct contact between nTreg and Teff cells is sufficient for nTreg cell-contact suppression. We first show that nTreg cell suppression is independent of APCs and their derived co-stimulatory signals. We then used a two-colour, lipid dye labelling and quantification approach to formally demonstrate that nTreg cells specifically form cell conjugates with responding T (Tresp) cells only under TCR activating conditions. Strikingly, activated CD4⁺ nTreg cells undergo progressive trogocytosis, a process by which membrane fragments are transferred from one cell subset to another, with Tresp cells more readily than Teff cells. These results are the first to show that nTreg cell cognate interactions with Tresp cells leads to trogocytosis between the cells, and the first to relate the degree of trogocytosis with the level of nTreg-mediated suppression.

Keywords::

• Trogocytosis
• Foxp3
• regulatory T-cell
• suppression
• peripheral tolerance
• mechanism

Acknowledgements

C.A.P and J. L. N. are holders of Canada Research Chairs.

Declaration of interest: C.A.P acknowledges the financial support of the Canadian Institutes for Health Research (CIHR MOP 67211). D. B. and J. L. N. acknowledge funding from the NanoIP programme of the Natural Sciences and Engineering Research Council, the CIHR Nanomedicine programme, and the CIHR Regenerative Medicine and Nanomedicine Team Grant. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.