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

Journal of Leukocyte Biology
Zhe ShaoHerbert Schwarz

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...Continue Reading

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Citations

May 4, 2016·Oncoimmunology·Bhushan DharmadhikariHerbert Schwarz
Feb 13, 2018·Biology of the Cell·Makoto NakashimaRyouichi Horie
Apr 27, 2019·Journal of Cellular Physiology·Meihui WuHerbert Schwarz
Oct 22, 2019·Frontiers in Immunology·Qun ZengHerbert Schwarz
Feb 1, 2020·Oncoimmunology·Khang LuuHerbert Schwarz
Apr 10, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jim Reed, Scott A Wetzel
Sep 17, 2020·Oncoimmunology·Qun Zeng, Herbert Schwarz

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