Trogocytic CD137 transfer causes an internalization of CD137 ligand on murine APCs leading to reduced T cell costimulation

Abstract

CD137 ligand (CD137L) is expressed on APCs and crosslinks CD137, a powerful costimulatory molecule on T cells during cognate interactions, and thereby greatly enhances immune responses. We report that CD137 can be transferred from activated T cells and from tumor cells that express CD137 to other cells via trogocytosis. This trogocytic transfer is independent of CD137L expression by the recipient cell. However, if CD137L is present on the recipient cell, the transferred CD137 binds to CD137L and the CD137-CD137L complex becomes internalized. The removal of CD137L from the surface of APCs lowers their ability to costimulate T cells, as evidenced by a reduced IFN-γ secretion. Removal of CD137L on APCs by trogocytic transfer of CD137 occurs within 1 h and requires cell-cell contact and the continuous presence of CD137-expressing cells. Bidirectional signaling exists for the CD137 receptor/ligand system, because CD137L also signals into APCs. We propose that the trogocytic transfer of CD137 from activated T cells to APCs and the subsequent removal of CD137L from APCs is a physiologic regulatory mechanism that limits immune activity. Furthermore, we hypothesize that the trogocytic transfer of CD137 occurs in cancers and quenches the activity of APCs, contributing to the cancer cells escaping immune surveillance. Taken together, our findings demonstrate that the trogocytic transfer of CD137 leads to an internalization of CD137L on APCs and a reduction in immune activity.

Keywords: IFN-γ; immune regulation.